Explain the anti-inflammatory and hyperglycemic actions of glucocorticoids.

Hyperglycemic action of glucocorticoids.

Glucocorticoids affect carbohydrates, lipid and protein metabolism. They increase synthesis of a number of key enzymes in gluconeogenesis pathway within hepatocytes. Although the actions of glucocorticoids on the liver are anabolic, the actions on skeletal muscle and adipose tissue are catabolic. Catabolic actions may result because glucose uptake of these tissues is inhibited by glucocorticoids. In the absence of a metabolic substrate for ATP production, proteolysis of muscle proteins and lipolysis of fat occurs. The free fatty acids (FFAs) and amino acids that are released from these tissues become available as substrate for gluconeogenesis within the liver.
The glucose produced is either stored as glycogen or released into the blood. Excessive secretion of glucocorticoid is antagonistic to the actions of insulin and predisposis the individual to diabetes mellitus as the actions of glucocorticoid elevate blood glucose levels. Glucocorticoid also reduce the affinity of certain cells for insulin, which further aggravate the diabetic hyperglycemia.

Anti-inflammatory actions of glucocorticoids.

At higher than physiological concentration, as in Cushing's disease, glucocorticoids inhibit inflammatory and allergic reactions. These actions may result from stabilization of lysosomal membranes that prevents the secretion of enzymes that normally occurs during inflammation. Glucocorticoid inhibit the infiltration of leukocytes into the affected tissue and also exert an immunosuppressive action through their lympholytic actions.

Glucocorticoids cause atrophy of the lymphatic system (lymph nodes, thymus gland, spleen) , which results in decreased levels of circulating lymphocytes. Ultimately, this lymphocytopenia results in failure of the body to provide antibodies during an injection. Although, glucocorticoid may be useful in combating the undesirable effects of local injections, excessive use of these agents may render the individual susceptible to severe systematic bacterial infection as many protective mechanisms are suppressed, but the underlying cause of the disease remains.

Interleukin-1 (IL-1), a member of a family of polypeptides produced by activated monocytes and other cells elicit a variety of physiological reactions observed during injection, inflammation and injury.

Stimulation of ACTH release may be one of these important non-immune responses that can be induced by monokine. Stimulation of ACTH release by IL-1-beta may contribute to a homeostatic regulation of the immune function. Increased hypothalamus--pituitary-adrenal activity results in an increased secretion of glucocorticoid that suppress immune responses and hence unfavorable overstimulation of the immune reaction, during injection.

Increased secretion of glucocorticoid would represent a way for the body's natural defense mechanism to control the undesirable symptoms such as arthritis, induced by increased production of IL-1-beta observed in Lyme disease.

Hence IL-1-beta play an important role as a carrier of messages from immune system to neuroendocrine system.