The Neuropeptide α‐MSH in HIV Infection and Other Disorders in Humans a

Abstract: We measured plasma concentration of α‐melanoctye‐stimulating hormone (α‐MSH), a proopiomelanocortin derivative that modulates pyrogenic and proinflammatory effects of cytokines, in infectious and inflammatory disorders in humans to learn if changes in this peptide take place in naturally occurring disease. α‐MSH was elevated in HIV‐infected patients of the CDC groups III and IV. Although the peptide increased in the circulation of normal subjects injected with endotoxin, it was reduced in patients with septic syndrome. α‐MSH was found in the synovial fluid of arthritis patients, and its concentration was greater in the forms of arthritis marked by greater inflammation. We found that α‐MSH is increased in the circulation of patients with acute myocardial infarction receiving thrombolitic therapy. Plasma concentrations of α‐MSH is increased in the circulation of patients with acute myocardial infarction receiving thrombolitic therapy. Plasma concentrations of α‐MSH were lower in healthy elderly subjects than in young controls. Because an excess of proinflammatory cytokines can have detrimental effects, we investigated the influences of α‐MSH on the production of interleukin‐1 (IL‐1) and tumor necrosis factor (TNF) in HIV‐infected patients and in patients with septic syndrome. Production of these cytokines in whole‐blood samples stimulated with endotoxin was significantly reduced by treatment of blood with α‐MSH. α‐MSH has been injected into at least 106 human subjects to study its effects on pituitary function, menstrual bleeding, and tanning. The peptide was always well tolerated. α‐MSH administration could open new perspectives in treatment of inflammatory diseases in humans.

[1]  J. M. Lipton,et al.  Anti-inflammatory actions of the neuroimmunomodulator α-MSH , 1997 .

[2]  J. M. Lipton,et al.  The neuropeptide α-MSH has specific receptors on neutrophils and reduces chemotaxis in vitro , 1996, Peptides.

[3]  J. B. Tatro Receptor biology of the melanocortins, a family of neuroimmunomodulatory peptides. , 1996, Neuroimmunomodulation.

[4]  J. M. Lipton,et al.  α‐MSH production, receptors, and influence on neopterin in a human monocyte/macrophage cell line , 1996 .

[5]  J. M. Lipton,et al.  Endotoxin Causes Release of α-Melanocyte-Stimulating Hormone in Normal Human Subjects , 1995 .

[6]  J. M. Lipton,et al.  Endogenous cytokine antagonists during myocardial ischemia and thrombolytic therapy. , 1995, American heart journal.

[7]  J. M. Lipton,et al.  The anticytokine neuropeptide alpha-melanocyte-stimulating hormone in synovial fluid of patients with rheumatic diseases: comparisons with other anticytokine molecules. , 1994, Neuroimmunomodulation.

[8]  W. Millington,et al.  Proopiomelanocortin‐Derived Peptides and mRNA Are Expressed in Rat Heart , 1993, Annals of the New York Academy of Sciences.

[9]  A. Fauci,et al.  Immunopathogenesis of HIV infection , 1991, Journal of acquired immune deficiency syndromes.

[10]  J. M. Lipton,et al.  Neuropeptide α-MSH antagonizes IL-6- and TNF-induced fever , 1991, Peptides.

[11]  A. Fauci,et al.  Viral antigen stimulation of the production of human monokines capable of regulating HIV1 expression. , 1989, Journal of immunology.

[12]  J. M. Lipton,et al.  Concentration of melanocyte stimulating hormone (MSH) within specific brain regions in aged squirrel monkeys , 1987, Brain Research Bulletin.

[13]  J. M. Lipton,et al.  Antipyretic potency of centrally administered alpha-melanocyte stimulating hormone. , 1983, Science.

[14]  J. M. Lipton,et al.  Plasma concentration of cytokine antagonists in patients with HIV infection. , 1994, Neuroimmunomodulation.

[15]  K. Tracey,et al.  Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. , 1994, Annual review of medicine.

[16]  J. M. Lipton,et al.  The neuropeptide alpha-melanocyte-stimulating hormone inhibits experimental arthritis in rats. , 1994, Neuroimmunomodulation.

[17]  A. Catania,et al.  alpha-Melanocyte stimulating hormone in the modulation of host reactions. , 1993, Endocrine reviews.

[18]  J. M. Lipton,et al.  Proopiomelanocortin-derived peptides and cytokines: relations in patients with acquired immunodeficiency syndrome. , 1993, Clinical immunology and immunopathology.

[19]  J. Justement,et al.  Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. , 1990, Proceedings of the National Academy of Sciences of the United States of America.