**3.2. Monocytes and macrophages**

GCs antagonize macrophage differentiation and inhibit many of their functions. GCs (1) supress myelopoiesis and inhibit expression of class II major histocompatibility complex antigens induced by interferon-γ; (2) block the release of numerous cytokines, such as interleukin-1, interleukin-6, and tumor necrosis factor-α; (3) suppress production and release of pro-inflammatory prostaglandins (PGs) and leukotrienes; (4) suppress phagocytic and microbicidal activities of activated macrophages; (5) reduce the clearance of opsonized bacteria by the reticuloendothelial system; (6) reduce accumulation of monocytes and macrophages in the tissues [28–31].

### **3.3. Eosinophils, basophils, and mast cells**

GCs support eosinophil apoptosis. In addition to this, GCs decrease the accumulation of eosinophils and mast cells to the allergic reaction sites. Also, GCs inhibit IgE-dependent release of histamine and leukotriene C4 from basophils, and they also inhibit degranulation both production of cytokines and degranulation of mast cells and eosinophils [26, 32, 33].

**3.9. Fibroblasts**

**3.10. Prostaglandins**

[47–53].

**4. Side effects of systemic glucocorticoids**

**Enhanced in patients with underlying risk factors or concomitant use of other drug**

**Onset early in therapy, essentially unavoidable**

• Enhanced appetite, weight gain, or both

**When supraphysiologic treatment is sustained**

• Hypothalmic-pituitary-adrenal suppression

• Emotional lability

• Diabetes mellitus

• Glucocorticoid-related acne

• Cushingoid appearance

• Impaired wound healing

At supraphysiological concentrations, GCs suppress proliferation of fibroblasts and growth factor-induced DNA synthesis and protein synthesis, including synthesis of collagen and glycosaminoglycan. Also GCs have been shown to interact with two mediators of fibroplasia; transforming growth factor-β and vascular endothelial growth factor. Furthermore GCs induce fibronectin messenger RNA transcription, inhibit interleukin-1, tumor necrosis factor-αinduced metalloproteinase synthesis, and arachidonic acid metabolite synthesis [20, 28, 45, 46].

Suppression of inflammatory prostaglandins (PGs) is a major factor in the anti-inflammatory action of the GCs. The suppression of phospholipase A2 activity with GCs is mediated by the activation of inhibitors of the enzyme itself or by inhibition of enzyme synthesis. The glucocorticoid-linked lipocortin/annexin family of proteins may be involved in this process. A second step in prostaglandin synthesis is the formation of prostaglandin H2 from arachidonic acid by enzymes called cyclooxygenases. The COX-2 gene and protein are strongly upregulated in endothelial cells, fibroblasts, and macrophages, and by mediators, such as endotoxin and interleukin-1. But GCs strongly suppress the expression of COX-2 induced by inflammatory stimuli. Later, D'Adamio et al. identified a glucocorticoid-induced leucine zipper (GILZ). GILZ is a member of the leucine zipper protein family which belongs to the transforming growth factor β-stimulated clone-22 family of transcription factors. GILZ inhibits inflammatory cytokine-induced expression of COX-2, by this way mediates the anti-inflammatory effects of GCs

Toxicity of GCs is one of the most common causes of iatrogenic illness associated with chronic inflammatory disorders. The side effects of GCs have been known for decades. But the exact risk-benefit ratio is incomplete and/or inconsistent, because usually it is difficult to differentiate the effects of GCs from the effects of the underlying accompanying diseases, other comorbidities,

• Insomnia

• Hypertension • Peptic ulcer disease

• Myopathy • Osteonecrosis

infections

• Increased susceptibility to

Side Effects of Glucocorticoids

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http://dx.doi.org/10.5772/intechopen.72019
