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Interleukin-8 (IL-8) production in vivo was monitored in four study groups: normal blood donors, patients with pulmonary tuberculosis (TB), patients with human immunodeficiency virus type 1 (HIV-1) infection, and dually infected (HIV/TB) patients. We show that whereas there was evidence of detectable levels of cell-associated IL-8 (mRNA and protein) in peripheral cells of healthy individuals, this was largely lost in the disease states studied. Coupled with this finding was significantly increased circulating levels of IL-8 in HIV-1-infected individuals with or without concomitant pulmonary TB (P &lt; 0.001). On the other hand, the capacity of peripheral mononuclear cells to produce IL-8 spontaneously ex vivo was enhanced in HIV-1 and TB patients (P &lt; 0.05) and many of the HIV/TB group, but their corresponding capacities to respond to various stimuli, in particular phytohemagglutinin, were significantly diminished compared to those of normal donors (P &lt; 0.05). Circulating levels of IL-8 in a group of HIV/TB patients were significantly positively correlated with the percentage of polymorphonuclear leukocytes (PMN) in the peripheral circulation (r = 0.65;P = 0.01), the proportions of IL-8 receptor A (IL-8RA)-expressing (r = 0.86;P &lt; 0.01) and IL-8RB-expressing (r = 0.77;P &lt; 0.01) PMN, and the capacity of PMN to migrate in response to IL-8 as chemoattractant (r = 0.68;P &lt; 0.01). IL-8RB fluorescence intensity, however, was negatively correlated with plasma IL-8 levels (r = −0.73;P &lt; 0.01). Our results suggest that altered regulation of IL-8 in HIV-1 may have important implications for antimicrobial defenses and for normal immune processes.

Dysregulated Production of Interleukin-8 in Individuals Infected with Human Immunodeficiency Virus Type 1 andMycobacterium tuberculosis