AEGiS-11IAC: TNF and TNF-related molecules in HIV-positive individuals: relationship with type 1 and type 2 response.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

Print this Article


TNF and TNF-related molecules in HIV-positive individuals: relationship with type 1 and type 2 response.

Int Conf AIDS 1996 Jul 7-12; 11:214 (abstract no. Th.A.162)
Rizzardi GP, Marriott JB, Cookson S, Meroni PL, Dalgleish AG, Barcellini W; Ospedale Policlinico, Milano, Italy. Fax: 02-5519-2842. E-mail: milancam@imiucca.csi.unimi.it.

OBJECTIVE: To study secretion in peripheral mononuclear cell (PBMC) cultures of TNF and TNF-related molecules from HIV-positive patients at different stage of disease, and to correlate them with type 1 and type 2 cytokine profiles.

METHODS: ELISA assays were used to measure sCD30, p24 and cytokine levels in unstimulated and PHA-stimulated cultures from 87 HIV-positive patients at different stages of disease. We determined CD30 antigen expression and membrane-bound TNF-alpha (mbTNF-alpha) by flow cytometry analysis.

RESULTS: Although we found that levels of sCD30 were non significantly increased in HIV-positive individuals, both in PHA-stimulated and unstimulated cultures, levels of PHA-stimulated sCD30 increased during progression (CDC 2 vs CDC 3, p=0.032; CDC 3 vs HIV-negative controls, p=0.07), whereas those of unstimulated cultures showed a decreasing trend with progression. Furthermore, in HIV-positive individuals a higher percentage of PBMCs expressed CD30 antigen and mbTNF-alpha than that in HIV-negative controls. Moreover, percentages of cells expressing CD30 molecule were positively correlated with levels of secreted TNF-alpha (r=0.92, p is less than 0.001), sCD8 (r=0.67, p=0.012), and IL-10 in PHA-stimulated cultures (r=0.85, p=0.002), which were significantly higher in HIV-positive subjects than in HIV-negative controls. An overall positive correlation was also found amongst PHA-stimulated levels of TNF-alpha, TNF-beta, IFN-y, and sCD8. Furthermore, mbTNF-alpha was positively correlated with values of PHA-stimulated TNF-alpha (r=0.57, p is less than 0.019) and CD30 antigen expression (r=0.92, p is less than 0.001), and with those of PHA-stimulated IL-10 at late stage of disease (r=0.94, p is less than 0.026). Finally, PHA-stimulated levels of p24 were negatively correlated with those of TNF-beta (r=0.27, p=0.047), and IFN-gamma (r=0.71, p is less than 0.001), and positively with those of sCD30 (r=0.46, p is less than 0.001) and IL-10 (r=0.43, p=0.018).

CONCLUSIONS: These results suggest that an inflammatory/cytotoxic response in conjunction with a type 1 cytokine response is associated with low viral burden, whereas TNF related molecules along with a type 2 response may be detrimental.

Keywords: AEGIS, Tumor Necrosis Factor, HIV Infections, Lymphotoxin, HIV Seropositivity, Phytohemagglutinins, Antigens, CD30, Interleukin-10, Viral Load, Cytokines, Receptors, Tumor Necrosis Factor, Antigens, CD, CD9 antigen, Human, ICA11KWDaegis,tumornecrosisfactor,hivinfections,lymphotoxin,hivseropositivity,phytohemagglutinins,antigens,cd30,interleukin-10,viralload,cytokines,receptors,tumornecrosisfactor,antigens,cd,cd9antigen,human,ica11

960707
ThA162

Copyright © 1996 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.