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Glucocorticoids are pleiotropic hormones that at pharmacologic doses prevent or suppress inflammation and other immunologically mediated processes. At the molecular level, glucocorticoids form complexes with specific receptors that migrate to the nucleus where they interact with selective regulatory sites within DNA; this results in positive and negative modulation of several genes involved in inflammatory and immune responses. At the cellular level, glucocorticoids inhibit the access of leukocytes to inflammatory sites; interfere with the functions of leukocytes, endothelial cells, and fibroblasts; and suppress the production and the effects of humoral factors involved in the inflammatory response. Clinically, several modes of glucocorticoid administration are used, depending on the disease process, the organ involved, and the extent of involvement. High doses of daily glucocorticoids are usually required in patients with severe diseases involving major organs, whereas alternate-day regimens may be used in patients with less aggressive diseases. Intravenous glucocorticoids (pulse therapy) are frequently used to initiate therapy in patients with rapidly progressive, immunologically mediated diseases. The benefits of glucocorticoid therapy can easily be offset by severe side effects; even with the greatest care, side effects may occur. Moreover, for certain complications (for example, infection diathesis, peptic ulcer, osteoporosis, avascular necrosis, and atherosclerosis), other drug toxicities and pathogenic factors overlap with glucocorticoid effects. Minimizing the incidence and severity of glucocorticoid-related side effects requires carefully decreasing the dose; using adjunctive disease-modifying immunosuppressive and anti-inflammatory agents; and taking general preventive measures.

Glucocorticoids have profound and complex effects on the human immune response. However, the precise mechanisms of the corticosteroid-induced immunoregulation in man have not been precisely defined. Intracytoplasmic corticosteroid-specific receptors appear to be an important common pathway for steroid-induced changes, but variations of receptor parameters do not account for the multifaceted effects on the immune system. Human circulating mononuclear cells redistribute out of the intravascular compartment following treatment with corticosteroids. Although certain components at this redistribution phenomenon have been well-characterized, the importance of this compartmental cellular shift with respect to the mechanisms of corticosteroid-induced immunoregulation are less well-defined. Recent observations that activated lymphocytes may be sensitive to the lytic effects of glucocorticoids suggest that under certain situations the elimination of selected subsets of cells may be a relevant mechanism of corticosteroid-mediated immunoregulation in man. Corticosteroid-mediated effects on monocyte function may be an important mechanism of drug-induced immunoregulation in monocyte-dependent responses. In some experimental conditions, corticosteroids inhibit Interleukin 1 production by monocytes. The immunoregulatory effects of corticosteroids on lymphocyte immune responses are complex. In vitro corticosteroids appear to selectively affect early immunoregulatory events as opposed to altering an established response. Multiple sites of steroid-induced modulations of human B cell responses have been defined.

Objective. Although the American College of Rheumatology (ACR) criteria for fibromyalgia are used to identify individuals with both widespread pain and tenderness, individuals who meet these criteria are not a homogeneous group. Patients differ in their accompanying clinical symptoms, as well as in the relative contributions of biologic, psychological, and cognitive factors to their symptom expression. Therefore, it seems useful to identify subsets of fibromyalgia patients on the basis of which of these factors are present. Previous attempts at identifying subsets have been based solely on psychological and cognitive features. In this study, we attempt to identify patient subsets by incorporating these features as well as the degree of hyperalgesia/ tenderness, which is a key neurobiologic feature of this illness.Methods. Ninety-seven individuals meeting the ACR criteria for fibromyalgia finished the same battery of self-report and evoked-pain testing. [degrees of freedom 6,89] ‫؍‬ 0.123, P < 0.0001), with univariate ANOVAs also indicating significant differences (all P < 0.05). One subgroup of patients (n ‫؍‬ 50) was characterized by moderate mood ratings, moderate levels of catastrophizing and perceived control over pain, and low levels of tenderness. A second subgroup (n ‫؍‬ 31) displayed significantly elevated values on the mood assessments, the highest values on the catastrophizing subscale, the lowest values for perceived control over pain, and high levels of tenderness. The third group (n ‫؍‬ 16) had normal mood ratings, very low levels of catastrophizing, and the highest level of perceived control over pain, but these subjects showed extreme tenderness on evoked-pain testing.Conclusion. These data help support the clinical impression that there are distinct subgroups of patients with fibromyalgia. There appears to be a group of fibromyalgia patients who exhibit extreme tenderness but lack any associated psychological/cognitive factors, an intermediate group who display moderate tenderness and have normal mood, and a group in whom mood and cognitive factors may be significantly influencing the symptom report.Fibromyalgia (FM) is a complex, contentious disease entity. It is currently defined by the 1990 American College of Rheumatology (ACR) classification criteria (1), in which an individual is required to have both a history of chronic widespread pain and the finding of