Cytokine and cytokine receptor concentrations in bone marrow supernatant from patients with HIV: Correlation with hematologic parameters

Background: To determine the concentrations of tumor necrosis factor (TNF)a lpha, soluble TNF receptors (sTNFR), interleukin (IL)-1 beta, gamma-interfe ron (IFN), macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and R ANTES to which hematopoietic progenitors are exposed in vivo in HIV patient s and the correlation of these concentrations with hematologic parameters, cytokine and cytokine receptor concentrations were measured by ELISA in bon e marrow aspirate supernatants from 19 HIV patients undergoing diagnostic e valuation and 14 healthy paid volunteer controls, IL-1 beta and gamma-IFN w ere rarely detectable. All cytokines/receptors detectable in marrow superna tant, except RANTES, showed mean concentrations 1.6- to 6.2-fold higher in patients with HIV compared to healthy controls. Methods: Elevated TNF-alpha and MIP-1 beta were associated with marrow invo lvement by lymphoma, Hodgkin disease, or mycobacterial infection, Concentra tions of all cytokines/receptors measured correlated with the severity of a nemia. CD8+ lymphocytes were inversely correlated with concentrations of al l cytokines measured other than MIP-1 alpha, To identify differences specif ic to HIV infection, marrow supernatant cytokine concentrations were also e valuated in 9 non-HIV patients undergoing diagnostic marrow examination. Si gnificant differences were observed in TNF alpha, MIP1 alpha, and IL-1 beta concentrations. Results: These studies demonstrate that concentrations of these cytokines a nd receptors are elevated in bone marrow supernatant of HIV-infected patien ts with hematologic abnormalities, and that these concentrations correlate with clinical parameters in these patients. Conclusions: Evaluation of local concentrations of cytokines may be relevan t to understanding tissue-specific pathology in HIV-infected individuals,