CYTOKINE MESSENGER-RNA EXPRESSION IN MONONUCLEAR-CELLS FROM DIFFERENTTISSUES DURING ACUTE SIVMAC251 INFECTION OF MACAQUES

We used semiquantitative RT-PCR to monitor the expression of mRNA enco ding cytokines (IL-1 beta, IL-6, TNF-alpha, and IL-10) and IFN-gamma i n fresh isolated peripheral blood mononuclear cells (PBMCs), lymph nod e mononuclear cells (LNMCs), and mononuclear cells obtained after bron choalveolar lavages (BALMCs), of four cynomolgus macaques inoculated i ntravenously with a pathogenic isolate of simian immunodeficiency viru s (SIVmac251). To investigate the effects of the viral load on the exp ression of the cytokines, two monkeys received 30 mg kg(-1) day(-1) of didanosine (ddI). The two nontreated monkeys became infected and sero converted, whereas the ddI-treated monkeys were completely protected a s demonstrated by all criteria of diagnosis of SIV infection, Concomit ant with the peak of viral replication (2 weeks after the experimental inoculation), high levels of IL-6 mRNA were produced in PBMCs, LNMCs, and BALMCs of the two placebo-treated infected monkeys, Overexpressio n of TNF-alpha and IL-10 mRNAs was sometimes observed in LNMCs and BAL MCs. A progressive overexpression of IFN-gamma mRNA, starting 2 weeks after experimental inoculation, was observed in BALMCs from infected a nimals. Concurrently, a marked increase in the CD8(+) lymphocyte perce ntage in the BAL fluids was detected by FAGS analysis. Thus, our resul ts emphasize the importance of a comparative study of the expression o f cytokines in different tissues, They suggest the interactions of mon ocyte/macrophage monokine production with viral replication, as well a s the role of IFN-gamma in the development of lung cellular immunity t o SIV infection.