Dysregulated production of interleukin-8 in individuals infected with human immunodeficiency virus type 1 and Mycobacterium tuberculosis

Interleukin-8 (IL-8) production in vivo was monitored in four study groups: normal blood donors, patients with pulmonary tuberculosis (TB), patients w ith human immunodeficiency virus type 1 (HIV-1) infection, and dually infec ted (HIV/TB) patients. We show that whereas there was evidence of detectabl e levels of cell-associated IL-8 (mRNA and protein) in peripheral cells of healthy individuals, this was largely lost in the disease states studied. C oupled with this finding was significantly increased circulating levels of IL-8 in HIV-1-infected individuals with or without concomitant pulmonary TB (P < 0.001). On the other hand, the capacity of peripheral mononuclear cel ls to produce IL-8 spontaneously ex vivo was enhanced in HIV-1 and TB patie nts (P < 0.05) and many of the HIV/TB group, but their corresponding capaci ties to respond to various stimuli, in particular phytohemagglutinin, were significantly diminished compared to those of normal donors (P < 0.05). Cir culating levels of IL-8 in a group of HIV/TB patients were significantly po sitively correlated with the percentage of polymorphonuclear leukocytes (PM N) in the peripheral circulation (r = 0.65; P = 0.01), the proportions of I L-8 receptor A (IL-8RA)-expressing (r = 0.86; P < 0.01) and IL-8RB-expressi ng (r = 0.77; P < 0.01) PMN, and the capacity of PMN to migrate in response to IL-8 as chemoattractant (r = 0.68; P < 0.01). IL-8RB fluorescence inten sity, however, was negatively correlated with plasma IL-8 levels (r = -0.73 ; P < 0.01). Our results suggest that altered regulation of IL-8 in HIV-1 m ay have important implications for antimicrobial defenses and for normal im mune processes.