Elevated concentrations of plasma α-melanocyte stimulating hormone are associated with reduced disease progression in HIV-infected patients,☆☆,

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Abstract

To determine whether concentrations of the anti-inflammatory peptide α-melanocyte stimulating hormone (α-MSH) are associated with accelerated or reduced disease progression in patients with HIV infection, plasma concentrations of α-MSH and two other anticytokine molecules, interleukin-1 receptor antagonist (IL-1 ra) and soluble tumor necrosis factor receptor (s TNF r), were taken repeatedly from HIV-positive patients over a 1-year period. Samples from 87 patients were collected by using special precautions to ensure accurate measurement of the peptide. α-MSH concentrations were determined by radioimmunoassay; IL-1 ra and s TNF r concentrations were measured by using enzyme-linked immunosorbent assays. Clinical and immunologic variables were recorded to determine whether there is an association between cytokine antagonist concentrations and disease progression. Elevated concentrations of circulating α-MSH were associated with reduced progression of the disease. Circulating α-MSH was greater in non-progressors than in progressors; the association between elevated α-MSH and reduced disease progression was even more pronounced in patients with baseline CD4+ T cell counts less than 200/μL. No such association was observed for the other two anticytokine molecules, and there was no significant correlation between the plasma concentration of either cytokine antagonist and α-MSH. The present evidence and previous findings indicate that elevated concentrations of α-MSH are associated with reduced disease progression in HIV-infected patients. (J Lab Clin Med 1999;133:309-15)

Section snippets

Patients

One-hundred-fifteen patients with HIV infection, 80 men and 35 women, were enrolled in the study. Their ages ranged from 25 to 61 years (mean 34.5). Risk behaviors were identified in 109 patients: 54 were current injection-drug users, 25 were former injection-drug users, and 30 had sexual behaviors associated with HIV transmission (21 had heterosexual, 8 homosexual, and 1 bisexual sexual experience). HIV infection diagnosis and classification were defined according to the guidelines established

Clinical and immunologic end points

Complete records over 10 to 12 months were available for 87 patients (65 men, 22 women; mean age 33.63 years). The data reported below are from these patients.

During the study, 33 patients (37.9%) showed immunologic or clinical progression of disease. Eleven of these progressors had a decrease in CD4+ T cells with absolute count <200 cells/μL, therefore reaching the immunologic end point. One of these patients also showed clinical progression (from CDC III to IV A for wasting syndrome), whereas

Discussion

The results show that elevated concentrations of circulating α-MSH are associated with reduced progression of the disease in HIV-infected subjects. Plasma concentrations of α-MSH were greater in non-progressors than in progressors; further, the association between elevated α-MSH and reduced disease progression was even more pronounced in patients with CD4+ T cells <200/μL at baseline. No such association was observed for two other anticytokine molecules, IL-1 ra and s TNF r, indicating that the

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    Supported by Grants 980.1.14 Progetto Terapia Antivirale/AIDS and 9403-30 IX Progetto AIDS from the Istituto Superiore di Sanità, Italy; and National Institutes of Health Grant NS10046 from the National Institute of Neurological Diseases and Stroke.

    ☆☆

    Reprint requests: Anna Catania, MD, Third Division of Internal Medicine (Padiglione Granelli), Ospedale Maggiore di Milano IRCCS, Via F. Sforza 35, 20122 Milano, Italy.

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