Imbalance in cytokine production by whole blood related to presence of cytopathogenic HIV-1 strains in HIV-1-infected patients.
The possible association between the emergence of cytopathogenic HIV-1 variants and disturbance of the cytokine production in the course of HIV-1 infection was studied in 18 infected patients. The cytopathogenicity of the isolates was studied in a microassay based on the use of HIV-1-infectible Hela-CD4 cells carrying the bacterial LacZ gene under the control of the HIV-LTR (P4 cells). In addition, the production of cytokines by heparinized whole blood (HWB) obtained the same day from HIV-1(+) patients was measured. TNF-alpha was determined in a one-step procedure combining HWB culture in the presence of LPS+PHA for 24 h and detection of cytokines in the same wells. In separate experiments HWB was cultured in the presence of LPS+PHA for 48 h, then the supernatants were collected and stored until assayed by ELISa for IFN-gamma and IL-4. Higher TNF-alpha levels were found in activated HWB of patients with cytopathic strains (n = 9) than in patients with non-cytopathic strains (n = 9, p = 0.02) assessed with P4 cells. A defective production of type 1 cytokine (IFN-gamma) and no increased secretion of type 2 cytokines (IL-4) was observed in patients with cytopathic strains. IFN-gamma/IL-4 ratios were significantly lower in patients with cytopathic strains (n = 9) than in other patients (n = 9, p = 0.009). The results show that the disarray of cytokine production, as assessed with whole blood culture, is associated with the cytopathogenicity of HIV-1 isolates in HIV-1-infected individuals.
Benyoucef
S
S
Laboratorie de Virologie, Institut Gernez Rieux, CHU, Lille, France.
Lion
G
G
Gérard
Y
Y
Wattré
P
P
De Groote
D
D
Hober
D
D
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000821:virology*; D000914:Antibodies, Viral / Q000097:blood; D015153:Blotting, Western; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D015847:Interleukin-4 / Q000097:blood*; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000914:Antibodies, Viral; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma