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In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
Cytokine and cytokine receptor concentrations in bone marrow supernatant from patients with HIV: correlation with
G Dallalio1, M North, S W McKenzie
1Division of Hematology/Oncology, Ralph H. Johnson VA Medical Center, Charleston SC, USA.
Insights
HIV patients exhibit elevated levels of inflammatory cytokines and receptors in bone marrow, correlating with hematologic abnormalities. These findings highlight the role of local cytokine concentrations in HIV-related tissue pathology.
Area of Science:
- Immunology
- Hematology
- Virology
Background:
- HIV infection is associated with various hematologic abnormalities.
- Cytokine profiles in the bone marrow microenvironment of HIV patients are not fully understood.
- Understanding local cytokine concentrations is crucial for elucidating HIV pathogenesis.
Purpose of the Study:
- To quantify specific cytokine and soluble receptor levels in bone marrow of HIV patients.
- To correlate these concentrations with hematologic parameters.
- To identify cytokine differences specific to HIV infection.
Main Methods:
- Bone marrow aspirate supernatants from 19 HIV patients and 14 healthy controls were analyzed.
- Enzyme-linked immunosorbent assay (ELISA) was used to measure concentrations of TNF-alpha, sTNFR, IL-1 beta, IFN-gamma, MIP-1 alpha, MIP-1 beta, and RANTES.
- Cytokine levels were compared between HIV patients and controls, and correlated with clinical and hematologic data.
Main Results:
- Mean concentrations of most measured cytokines/receptors (except RANTES) were significantly higher (1.6- to 6.2-fold) in HIV patients compared to controls.
- Elevated TNF-alpha and MIP-1 beta were linked to marrow involvement by lymphoma, Hodgkin disease, or mycobacterial infection.
- All measured cytokines/receptors, except MIP-1 alpha, correlated with anemia severity, and CD8+ lymphocytes were inversely correlated with most cytokines.
Conclusions:
- Cytokine and receptor concentrations are elevated in the bone marrow of HIV-infected individuals with hematologic abnormalities.
- These elevated levels correlate with clinical parameters, suggesting a role in HIV-related pathology.
- Assessing local cytokine concentrations offers insights into tissue-specific pathology in HIV infection.
Background:
To determine the concentrations of tumor necrosis factor (TNF) alpha, soluble TNF receptors (sTNFR), interleukin (IL)-1 beta, gamma-interferon (IFN), macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES to which hematopoietic progenitors are exposed in vivo in HIV patients and the correlation of these concentrations with hematologic parameters, cytokine and cytokine receptor concentrations were measured by ELISA in bone marrow aspirate supernatants from 19 HIV patients undergoing diagnostic evaluation and 14 healthy paid volunteer controls. IL-1 beta and gamma-IFN were rarely detectable. All cytokines/receptors detectable in marrow supernatant, 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 involvement by lymphoma, Hodgkin disease, or mycobacterial infection. Concentrations of all cytokines/receptors measured correlated with the severity of anemia. CD8+ lymphocytes were inversely correlated with concentrations of all cytokines measured other than MIP-1 alpha. To identify differences specific to HIV infection, marrow supernatant cytokine concentrations were also evaluated in 9 non-HIV patients undergoing diagnostic marrow examination. Significant differences were observed in TNF alpha, MIP-1 alpha, and IL-1 beta concentrations.
Results:
These studies demonstrate that concentrations of these cytokines and receptors are elevated in bone marrow supernatant of HIV-infected patients with hematologic abnormalities, and that these concentrations correlate with clinical parameters in these patients.
Conclusions:
Evaluation of local concentrations of cytokines may be relevant to understanding tissue-specific pathology in HIV-infected individuals.
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