Using a specific antiserum recognizing recombinant rat interleukin-1 beta (IL-1 beta), immunoreactive material was localized to cytoplasmic granules in anterior pituitary endocrine cells and colocalized with TSH in thyrotropes. Authenticity was established by Northern blot hybridization using a specific rat IL-1 beta cRNA probe, revealing a 1.8-kilobase mRNA identical to that in the spleen. The marked increase in anterior pituitary IL-1 beta message after the administration of bacterial lipopolysaccharide, raises the possibility that IL-1 beta may be involved in paracrine or autocrine regulation of pituitary function during infectious challenge.
Obesity may be an independent risk factor for coronary artery disease and contribute to a chronic state of systemic inflammation leading to atherosclerosis and metabolic abnormalities, such as diabetes, insulin resistance, dyslipidemia and hypertension. Visceral fat, in fact, may act as an endocrine organ, synthesizing and releasing atherogenic inflammatory cytokines, whose circulating levels depend on the individual's nutritional state, and the extent and anatomical location of fat stores. Unsuspected viral infections might also be involved in enhancing autocrine/paracrine mechanisms of cytokine release from omental fat. Elevated levels of blood cytokines may interact with the neuroendocrine system, autonomic nerves and peripheral lymphatic organs. This may lead to local inflammatory reactions in many body compartments, in particular in the heart tissue, possibly affecting the process of circulatory recovery in obese subjects, and predisposing these patients to a greater risk of myocardial inflammatory disease than individuals with normal body mass index. Circulating levels of inflammatory cytokines might be considered to determine risk categories for development of cardiovascular complications in obese subjects. In addition, their reduction with pharmacological antagonists might prevent and/or control acute cardiovascular events and increase energy expenditure in obese patients, especially after surgical treatment, through reduction of cytokine inhibition of the hypothalamic-pituitary-thyroid axis.
A 44-yr-old man with hypocortisolism was shown to have an undetectable basal plasma ACTH level and absent or subnormal ACTH and beta-lipotropin responses to provocative testing with insulin, vasopressin, and CRH. Endocrine function after glucocorticoid replacement was otherwise normal, thus establishing the diagnosis of isolated ACTH deficiency. This patient's serum was tested immunohistochemically for the presence of an antipituitary antibody by indirect immunofluorescence of rat pituitary tissue. Positive immunostaining was observed in stellate-shaped cells in the anterior and intermediate lobes. Immunopositive cells were shown by immunoelectron microscopy to have ultrastructural characteristics of corticotrophs. Immunoreactivity was concentrated in secretory granules 120-170 nm in diameter. In a double immunolabeling procedure, staining by the patient's serum was shown to colocalize with rabbit antiserum to ACTH, but not with antisera to PRL, GH, beta TSH, or beta LH. Immunoabsorption of the patient's serum with ACTH-(1-24), ACTH-(1-39), gamma MSH, corticotropin-like intermediate lobe peptide, beta-endorphin, or beta-lipotropin failed to diminish immunolabeling in the pituitary. We conclude that the antipituitary antibody in this patient's serum shows immunohistochemical specificity for a rat corticotroph antigen located in secretory granules that is neither ACTH nor any of the proopiomelanocortin (POMC)-derived peptides tested. The autoantigen could be a cell-specific granular factor involved in the posttranslational processing of POMC or secretion of ACTH. We postulate that an autoimmune process may account for this patient's disease, and that his antipituitary antibody could play a pathogenic role by either inhibiting a POMC-processing enzyme or initiating an antibody-dependent cell-mediated cytotoxicity reaction, resulting in the selective destruction of corticotrophs.
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