GLUCOCORTICOID

EFFECTS ON THE IMMUNE SYSTEM

Jaichat Mekaroonkamol, MD.

OUTLINES
Introduction
Synthesis and action
Effects on immune systems
Impact on vaccination
Impact of dose
Infection risk

CORTISONE AS A SYMPTOMATIC
TREATMENT OF RHEUMATOID ARTHRITIS

STEROID IN CLINICAL USED

Allergic and respiratory disorders
Anaphylactic shock , atopic dermatitis , asthma , chronic rhinitis , chronic
bronchitis , emphysema

Autoimmune disorders
Rheumatoid arthritis , systemic lupus erythematosus , systemic vasculitis ,
polymyalgia rheumatica , temporal arteritis , autoimmune hemolysis ,
myasthenia gravis , Graves ophthalmopathy

Dermatologic disorders
Eczema , contact dermatitis , irritant dermatitis , stasis dermatitis ,
seborrheic dermatitis , exfoliative dermatitis , psoriasis , lichen striatus ,
lichen planus , lichen nitidus , vitiligo , pruritus ani

Williams Textbook of Endocrinology, 1998; 517-

STEROID IN CLINICAL USED

Gastrointestinal disorders
Ulcerative colitis , Crohns disease , chronic active hepatitis , subacute
hepatic necrosis , alcoholic hepatitis , non-alcoholic cirrhosis

Renal disorders
Nephrotic syndrome , lupus nephritis , rapid progressive glomerulonephritis

Malignancies
Lymphoma , leukemia , breast cancer

Graft rejection
Kidney , heart , lung , liver and other tissue transplantation

Others
Sarcoidosis, vitamin D intoxication , septic shock , cerebral edema , spinal
cord injury , hypercalcemia , Bells palsy, conjucntivitis , keratitis , etc.

Williams Textbook of Endocrinology, 1998; 517-

SYNTHESI
S

SYNTHESIS
Adrenal production of HC and aldosterone
Cholesterol progenolone intermediate
progesterone hydroxylate at 17-,21-, and 11positions HC

High dose GC >1 wk suppress HPA axis

IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

Neuroendrocrine
regulation of
inflammation
Hyperactivity of
HPA: Cushings
syndrome, stress
Immunosuppres
sion

Decrease HPA
Severe
inflammation

Rhen T et al. N Engl J Med 2005;353:1711-23

Oral and topical GCs pass rapidly through the

cell membrane by passive diffusion into the
cytoplasm

Genomic
effects
Nongenomic
effects

Glucocorticoid
receptor

Rhen T et al. N Engl J Med 2005;353:1711-23

GLUCOCORTICOID
RECEPTOR
Intracellular receptor
Member of the nuclear receptor family
Present in virtually all cells, including
those of the immune system
Highest affinity for dexamethasone

IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

Bind GR
Direct genomic effects

Rhen T et al. N Engl J Med 2005;353:1711-23

Enables GR to
associate with
transcriptional
coactivators or
repressors
Indirect genomic
effects

Rhen T et al. N Engl J Med 2005;353:1711-23

Rhen T et al. N Engl J Med 2005;353:1711-23

HUMAN HR PROTEIN
hGR
Primary form of GR
Vary expression
between cell type

Bind GCs
If reduced by up to 70%
not enough to prevent
effective
antiinflammatory
response

hGR
Lacks a ligand-binding
domain
Does not bind GCs
Increase expression in
GCs resistant and
decrease ability of hGR
to bind to GRE

IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

MECHANISM OF ACTION

IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

Nongenomic
effects

Genomic
effects
Direct effects
Indirect effects
Rhen T et al. N Engl J Med 2005;353:1711-23

TRANSCRIPTION

TRANSCRIPTION

GENOMIC MECHANISM
DIRECT EFFECTS
Binding of the receptor to GREs may result
in either enhancement or suppression of
transcription of susceptible downstream
genes

IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

Interactions between the cortisol

glucocorticoid receptor complex and
other transcription factors, such as
nuclear factor B (NFB)

Genomic
effects
Indirect effects
Rhen T et al. N Engl J Med 2005;353:1711-23

IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

GC activation antiinflammatory gene expression

Barnes. Br J pharmacol: Respiratory Pharmacology Issue Revised. 2010

GC suppression of activated inflammatory gene

expression

Barnes. Br J pharmacol: Respiratory Pharmacology Issue Revised. 2010

Middletons Allergy, 8th ed

MECHANISM OF ACTION

IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

NON-GENOMIC MECHANISM

Rhen T et al. N Engl J Med 2005;353:1711-23.

Inhibit prostaglandin
production
Induction and
activation of
annexin I
Induction of MAPK
phosphatase 1
Repression of
transcription of
cyclooxygenase 2

 The dosage is
increased up to
approximately
200 to 300 mg of
prednisone
equivalent per
day
Negative
feedback of
ACTH production
Inhibit effect on
lymphocyte
activation

Buttgereit F et al. Arthritis Rheum 41:761767, 1998.

 Membrane-bound receptors
The antianaphylacticactions of
glucocorticoids may be
explained by this mechanism.

Buttgereit F et al. Arthritis Rheum 41:761767, 1998.

Cassidy. Textbook of pediatric rheumatology. 5 th edition

OUTLINES
Introduction
Synthesis and action
Effects on immune systems
Impact on vaccination
Impact of dose
Infection risk

EFFECTS ON IMMUNE SYSTEMS

Effects on
leukocyte
trafficking
Effects on innate
immunity
Effects on acquired
immunity

IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

EFFECTS ON LEUKOCYTE
TRAFFICKING
Glucocorticoids have profound effects on the
cellular functions of leukocytes and endothelial cells
Reduced ability of leukocytes to adhere to vascular
endothelium and exit from the circulation.
Entry to sites of infection and tissue injury is impaired

suppression of the inflammatory

response
Fauci AS et al. Ann Intern Med 1976; 84:304.
Fauci AS et al. Cell Immunol 1980; 49:43.
Boumpas DT et al. Ann Intern Med 1993; 119:1198.

EFFECTS ON LEUKOCYTE
TRAFFICKING
Reduction in endothelial adhesion
Direct effects
on expression of adhesion molecules on both
leukocytes and endothelial cells

Indirect effects
the inhibitory effects of glucocorticoids on transcription
of cytokines(IL-1/TNF) that upregulate endothelial
adhesion molecule expression.

Fauci AS et al. Ann Intern Med 1976; 84:304.

Fauci AS et al. Cell Immunol 1980; 49:43.
Boumpas DT et al. Ann Intern Med 1993; 119:1198.

EFFECTS ON LEUKOCYTE
TRAFFICKING
Increased numbers of circulating neutrophils 1,2
Neutrophil migration through the vasculature to sites of
inflammation is severely impaired
Enhanced release of cells from the bone marrow
Inhibition of neutrophil apoptosis

Circulating levels of eosinophils are markedly and rapidly

reduced3
Sequestration of eosinophils in extravascular tissues, possibly due to
the preferential upregulation of the CXCR44
Induce apoptosis of eosinophils5
notably dexamethasone
1. Fauci AS et al. Ann Intern Med 1976; 84:304
2. Cox G. J Immunol 1995; 154:4719
3. Andersen V et al. Cell Tissue Kinet 1969; 2:139
4. Nagase H et al. J Allergy Clin Immunol 2000; 106:1132
5. Meagher LC et al. J Immunol 1996; 156:4422

EFFECTS ON LEUKOCYTE
TRAFFICKING
Tissue accumulation of monocytes and
macrophages is reduced
Decreased migration from the vasculature
Reduced elaboration of macrophage migration inhibition
factor

The numbers of circulating T lymphocytes are

rapidly reduced and B lymphocyte numbers are
reduced to a lesser extent

Gerlag DM et al. Arthritis Rheum 2004; 50:3783

Balow JE et al. J Exp Med 1973; 137:103

EFFECTS ON INNATE
IMMUNITY

EFFECTS ON INNATE IMMUNITY

PHAGOCYTES
Neutrophils
In vitro studies: inhibit neutrophil apoptosis1,2
Neutrophil phagocytic responses or bactericidal
activities do not appear to be significantly
impaired, although, at high doses, phagocytic
function may be inhibited3,4
The main impact: impairment of migration to
sites of inflammation or infection

1. Fauci AS et al. Ann Intern Med 1976; 84:304

2. Meagher LC et al. J Immunol 1996; 156:4422
3. Jones CJ et al. Ann Rheum Dis 1983; 42:56
4. Herzer P et al. Immunobiology 1980; 157:78

EFFECTS ON INNATE IMMUNITY

PHAGOCYTES
Eosinophils
Promote eosinophil apoptosis
attenuating synthesis of interleukin-5 (IL-5), a cytokine
that promotes eosinophil survival. 1,2

Variable inhibitory effects upon the

degranulation of eosinophils that are dependent
upon the activating ligand and the
glucocorticoid used in the assay3
Methylprednisolone inhibited degranulation of
normodense eosinophils up to 20%, hypodense
eosinophils up to 30%
1. Meagher LC et al. J Immunol 1996; 156:4422
2. Wallen N et al. J Immunol 1991; 147:3490
3. Kita H et al. J Allergy Clin Immunol 1991; 87:70

EFFECTS ON INNATE IMMUNITY

PHAGOCYTES
Monocytes and macrophages
Diminish the production of
monocyte/macrophage-derived eicosanoids and
inflammatory cytokines (IL-1, TNF, IL-6)1
Inhibit macrophage phagocytic and microbicidal
function2
Clearance of opsonized bacteria by the
reticuloendothelial system is reduced 3
Reduce Intracellular killing of Nocardia, Listeria,
and Salmonella4
1. Fauci AS et al. Ann Intern Med 1976; 84:304
2. Rinehart JJ et al. N Engl J Med 1975; 292:236
3. Atkinson JP et al. Blood 1974; 44:629
4. IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

EFFECTS ON INNATE IMMUNITY

MAST CELL & BASOPHILS
In vitro: inhibit both production of
cytokines and degranulation by mast cells.
The noted inhibition of inflammatory cytokine
production
suppression of gene transcription

The inhibition of mast cell degranulation

upregulation of inhibitory regulators of signaling, such
as SLAP1 (src-like adapter protein-1)

Prednisolone treatment in vivo reduces airway

basophilia
Andrade MV et al. J Immunol 2004; 172:7254
Nakamura R et al. Immunol Lett 2005; 98:272
Park SK et al. Mol Immunol 2009; 46:492
IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

EFFECTS ON INNATE IMMUNITY

PROINFLAMMATORY MEDIATORS
Degrade bradykinin, which is a vasodilatory
peptide central to the generation of some forms
of angioedema
Upregulating the synthesis of angiotensinconverting enzyme and neutral-endopeptidase
enzymes

Borson DB et al. Am J Physiol 1991; 260:L83

EFFECTS ON INNATE IMMUNITY

PROINFLAMMATORY MEDIATORS
Suppressing production of inflammatory
eicosanoids in phagocytic cells
inducing the synthesis of lipocortin-1 (annexin
I), macrocortin, and/or lipomodulin, all of which
inhibit phospholipase A2 (PLA2)-mediated
liberation of arachidonic acid from membrane
phospholipids

Flower RJ et al. Nature 1979; 278:456

Hirata F et al. Proc Natl Acad Sci U S A 1980; 77
Kim SW et al. J Biol Chem 2001; 276:15712

EFFECTS ON INNATE IMMUNITY

PROINFLAMMATORY MEDIATORS
Suppressing the synthesis of
cyclooxygenase-2 (COX-2)1
suppression of nuclear factor kappa B (NF-kB)
transcription.

Glucocorticoids do not appear to affect the

synthesis of constitutive cyclooxygenase12.

1 Chen CC et al. J Immunol 2000; 165:2719

2 Chatham WW, UpToDate 2014

EFFECTS ON IMMUNE SYSTEMS

Effects on
leukocyte
trafficking
Effects on innate
immunity
Effects on acquired
immunity

IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

EFFECTS ON ACQUIRED
IMMUNITY

EFFECTS ON ACQUIRED IMMUNITY

ANTIGEN PRESENTING CELLS
Dendritic cells and macrophages
Suppress expression of MHC II molecules on
macrophages1,2
Decrease the numbers of both circulating and
organ-resident dendritic cells3
Induced apoptosis of resident dendritic and/or
CD34+ precursor-derived CD14+ dendritic cells
4

1 van de Garde MD et al. J Immunol 2014; 192:1196

2 Schwiebert LM et al. Cell Immunol 1995; 165:12
3 Shodell M et al. Lupus 2003; 12:222
4 Woltman AM et al. J Immunol 2002; 168:6181

EFFECTS ON ACQUIRED IMMUNITY

T CELLS
Enhanced circulatory emigration 1 ( upregulate CXCR4)
Induction of apoptosis depend upon the stage of T
cell differentiation and T cell subtype

1 Fauci AS et al. Ann Intern Med 1976; 84:304

2 Ashwell JD et al. Annu Rev Immunol 2000; 18:309
3 Cohen JJ et al. J Immunol 1984; 132:38
4 Lanza L et al. Clin Exp Immunol 1996; 103:482

EFFECTS ON ACQUIRED IMMUNITY

T CELLS
T cell lineage commitment
inhibit the acute generation of both Th1- and
Th2-derived cytokines by activated T cells

Th1
IL-2
IL-3
TNF-
IFN-

Th2
IL-4
IL-5
IL-6
IL-13
Franchimont D et al. Regul Pept 1998; 73:59

EFFECTS ON ACQUIRED IMMUNITY

T CELLS
T cell lineage commitment
attenuate peripheral blood mononuclear cell
production of IL-12
Undifferentiated T cells to the Th1 and Th17
lineage
minimal effect on production of IL-10

Visser J et al. Blood 1998; 91:4255

Weaver CT et al. Immunity 2006; 24:677

Weaver CT et al. Immunity 2006; 24:677

EFFECTS ON ACQUIRED IMMUNITY

T CELLS
Regulatory T cell
Enhance the induction of IL-10 expression
Enhance transcription factor Foxp3+ (alone or vitamin
D3)
Dramatic potentiation of CTLA4 expression
CTLA4 contain ITIM and may be centrally involved in T
cell tolerance
Induction by steroids of CTLA-4 and Treg cell could
therefore potentiate tolerogenic response of T cells

IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

EFFECTS ON ACQUIRED IMMUNITY

B CELLS AND ANTIBODY PRODUCTION
Reduced numbers of circulating B lymphocytes
but to a much lesser extent than those of T cells 1

Synthesis of antibodies by B cells remains essentially unchanged following short-term administration 2

but mild to modest decreases in serum immunoglobulin G (IgG) levels have been observed following short (eg, two to four
week) courses of glucocorticoids

Enhancing effects of glucocorticoids on IL-4 induced B cell isotype switching to IgE 3

Inhibit seasonal increase in IgE level in AR Pt 4

1 Slade JD et al. J Lab Clin Med 1983; 101:479

2 Settipane GA et al. J Allergy Clin Immunol 1978; 62:162
3Jabara HH et al. J Immunol 1991; 147:1557
4 IAN M. ADCOCK and KIAN FAN CHUNG. Middletons Allergy, 8th ed

Bohle b et al. Clinical and Experimental Immunology,1995;101:474-479

 A 54-year-old female schoolteacher

nasal congestion, nasal polyposis requiring 3
polypectomies,chronic sinusitis, and a 40year history of asthma.
Medications at the time of evaluation
Methylprednisolone 4 to 8 mg/d for 36
years
Montelukast 10 mg/d
Albuterol as needed for wheezing
Alendronate, 10 mg/d
Calcium 200 mg/d, vitamin D 0.125 mg/d.
Fedor ME et al. Ann Allergy Asthma Immunol 2006; 97:113

EFFECTS ON IMMUNE SYSTEMS

These abnormalities resolved within 2 years

after tapering of corticosteroid therapy
Fedor ME et al. Ann Allergy Asthma Immunol 2006; 97:113

OUTLINES
Introduction
Synthesis and action
Effects on immune systems
Impact on vaccination
Impact of dose
Infection risk

IMPACT ON VACCINATION

14 adult steroid-dependent asthmatics

receiving daily or alternate day prednisone, 10
to 35 mg
14 age-matched nonsteroid dependent asthmatic
patients
polysaccharide antibody levels against serotypes
3, 7F, 9N, and 14

All patients either had or developed levels >

or = 300 ng Ab N/mL against one or more
pneumococcal serotypes after 4 week
immunization
Lahood N et al. Ann Allergy. 1993 Apr;70(4):289-94

27 steroid-responsive and six steroid-resistant

patients with nephrotic syndrome
12 age-matched control subjects

Significantly depressed in steroid-resistant

patients
Steroid-responsive nephrotic children who were
not receiving corticosteroid therapy at the time
of vaccination had significantly higher antibody
concentrations compared with control subjects
Fewer steroid-responsive patients receiving
corticosteroids achieved antibody concentrations
greater than or equal to 200 ngN/ml against type
19F
Spika JS et al. Pediatrics. 1982 Feb;69(2):219-23

32 healthy volunteers
62 patients with systemic lupus erythematosus
(SLE), rheumatoid arthritis, degenerative joint
disease, and other rheumatic diseases.
examined at the time of immunization and one
week, three weeks, and four months later
Administration of these vaccines was safe in
these patients with stable disease and induced
antibody responses in most individuals.
Antibody responses to A/New Jersey/76 were
significantly lower in young patients taking
glucocorticoids compared to those not taking
glucocorticoids.
Herron A et al. JAMA. 1979 Jul 6;242(1):53-6

influenza HA1 (A/Beijing), HA2 (A/Taiwan), and HB (B/Panama )

A without corticosteroid therapy

B oral corticosteroid therapy : median corticosteroid dose 10.0
mg/day (2.525 mg/day), equivalent to prednisolone)
C inhaled corticosteroid therapy: median inhaled corticosteroid
dose: 800 g/day (4001600 g/day), equivalent to budesonide)
Sumito Inoue et al. EXCLI Journal 2013;12:760-765

control

OCS

ICS

Sumito Inoue et al. EXCLI Journal 2013;12:760-765

IMPACT ON VACCINATION
In patients who do show evidence of
impaired vaccine response, removal of
chronic low-dose glucocorticoid treatment
may result in improved antibody
production

Fedor ME et al. Ann Allergy Asthma Immunol 2006; 97:113

IMPACT ON VACCINATION
Immunosuppression due to chronic
glucocorticoid use is a contraindication to
the administration of live virus vaccines,
such as measles, mumps, rubella (MMR),
varicella, and vaccinia (small pox).

CDC 2011
Chatham WW et al. UpToDate 2014

LIVE VIRUS VACCINES

OUTLINES
Introduction
Synthesis and action
Effects on immune systems
Impact on vaccination
Impact of dose
Infection risk

IMPACT OF DOSE
Some immunologic effects of glucocorticoids
are dose dependent
variable affinity of target genomic sites for the
complex of glucocorticoid and glucocorticoid
receptor
Administration of high-dose pulse glucocorticoids
may result in nonspecific general disruption of gene
transcription
may also have more rapid effects on leukocyte
aggregation, possibly as a consequence of effects on the
expression of leukocyte adhesion molecules and disruption
of calcium flux across membranes
Hammerschmidt DE et al. J Clin Invest 1979; 63:798
Youssef P et al. J Rheumatol 1995; 22:2065

IMPACT OF DOSE
LOW TO MODERATE DOSES
Less than 2 mg/kg per day of prednisone in
children or less than 40 mg per day in adults

T lymphocytes may be slightly reduced in the

circulation
CD4-positive cells more than CD8-positive T cells1
Delayed-type hypersensitivity (DTH) responses may
be impaired2
the failure of inflammatory cells to be recruited to
the site of the reaction cutaneous anergy

1 Haynes BF et al. J Clin Invest 1978; 61:703

2 Chatham WW et al. UpToDate 2014

 We treated two groups of six patients with classic RA with either

one or three daily 1 gm intravenous doses of MPS
Measured the immune response and clinical activity over 16
weeks.

Lymphopenia developed within two hours , peaked at

six hours and resolved by 24 hours with both
regimens.
Patients were followed for 16 weeks
PPD was unaffected, serum immunoglobulin levels
were unchanged, and primary antibody responses
to antigens were normal
Higher and repeated doses of MPS caused neither
greater lymphocytopenia nor more prolonged
suppression of recirculating lymphocytes than the
conventional oral doses.

Fan PT et al. J Lab Clin Med 1978; 91:625

OUTLINES
Introduction
Synthesis
Effects on immune systems
Impact on vaccination
Impact of dose
Infection risk

INFECTION RISK
SYSTEMIC GLUCOCORTICOID THERAPY
Dose-dependent increase: inhibitory
effects on phagocytic cell function.
With long-term, low-dose use, effects on
phagocytic cell function are minimal, but
there may be some inhibition of adaptive
immune responses with increasing
duration of therapy.

Chatham WW et al. UpToDate 2014

INFECTION RISK
INHALED AND TOPICAL CORTICOSTEROID
Inhaled and topical corticosteroids are
usually not implicated in increased risk of
systemic infections

Chatham WW et al. UpToDate 2014

INFECTION RISK
Various patient-specific factors influence infection
risk
underlying disorder
presence of concomitant immunosuppressive therapies
patient is hospitalized.

patients taking glucocorticoids may not manifest

signs and symptoms of infection as clearly, due to
the inhibition of cytokine release and associated
reduction in inflammatory and febrile responses.
This can impair early recognition of infection.

Chatham WW et al. UpToDate 2014

INFECTION RISK
A meta-analysis of controlled trials in
which glucocorticoids or placebo were
given
infection occurred significantly more often with
steroid therapy (12.7 versus 8.0 percent with
placebo, relative risk 1.6)
average dose of prednisone of more than 10
mg/day or a cumulative dose of greater than
700 mg.

Stuck AE et al. Rev Infect Dis 1989; 11:954

INFECTION RISK
223 patients with lupus who were not
receiving other immunosuppressive agents
The risk of infection rose from 1.5-fold at
an average prednisone dose below 10
mg/day to over eightfold in patients
receiving doses above 40 mg/day.

Ginzler E et al. Arthritis Rheum 1978; 21:37

INFECTION RISK
TYPES OF INFECTIONS
Herpes zoster
more commonly among patients taking lowdose
A retrospective cohort analysis of over 200
patients with RA found that eight patients
treated with glucocorticoids developed zoster
compared with only one control1
However, people receiving glucocorticoid may
have had closer surveillance, potentially leading
to more cases of herpes zoster detected.

1 Saag KG et al. Am J Med 1994; 96:115

INFECTION RISK
TYPES OF INFECTIONS
Tuberculosis
concern in patients receiving moderate to high
doses of glucocorticoids for prolonged periods
of time

Reactivation of latent Strongyloides

hyperinfection syndrome that can be fatal

Other helminthic or protozoan infections

unusual, except in areas of the world where they are
endemic (eg, P. falciparum).

Chatham WW et al. UpToDate 2014

INFECTION RISK
TYPES OF INFECTIONS
Opportunistic infections
only in patients with very significant
immunosuppression
prolonged glucocorticoids+immunosuppressant drugs
underlying immunosuppressive conditions

Pneumocystis carinii (P. jirovecii) pneumonitis is

associated with the use of glucocorticoids, both
with chronic use of moderate doses and shortterm use of high doses

Chatham WW et al. UpToDate 2014

INFECTION RISK
MEASURES TO REDUCE RISK
Use of short-acting preparations (such as
prednisone) given every other day
In one retrospective report of 70 patients
with various inflammatory conditions
treated with alternate day prednisone at
mean doses of 45 to 60 mg daily, none
developed serious infections

Fauci AS et al. Ann Intern Med 1976; 84:304.

TAKE HOME MESSAGE (1)

Diffuse across the cell membrane and bind to the
intracellular GR to form a complex that
translocates into the nucleus.
Genomic and Non-Genomic mechanism
Neutrophilic leukocytosis, accompanied by
dramatic reductions in circulating eosinophils,
monocytes, and lymphocytes
Effects on the innate immune system include
dose-dependent impaired phagocyte function and
attenuated production of proinflammatory
mediators.

TAKE HOME MESSAGE (2)

Glucocorticoids impair a variety of T cell functions
and induce T cell apoptosis.
B cells are less affected and antibody production
is largely preserved, although a mild decrement
in immunoglobulin G (IgG) and immunoglobulin A
(IgA) levels may develop in some patients with
chronic use.
Immunoglobulin E (IgE) levels may increase.

TAKE HOME MESSAGE (3)

Vaccine responses are preserved in most patients
on chronic low to moderate doses of
glucocorticoids, although the titers may be
reduced in some individuals.
Low to moderate dose may be impairedIn T cell
function but immunoglobulin levels are usually
normal or only slightly low.
High-dose, short-term pulse therapy results in
dramatic changes in levels of circulating
leukocytes, but relatively intact immunologic
functions immediately after administration

TAKE HOME MESSAGE (4)

Systemic glucocorticoid therapy is associated
with a dose-dependent increase in the risk of
infection
common viral, bacterial, and fungal pathogens
Opportunistic infections are less common, and
are mainly a concern in patients taking other
immunosuppressive agents or with diseases
causing immunocompromise.