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Infection and Immunity, March 1999, p. 1251-1260, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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

Stephen Meddows-Taylor, Desmond J. Martin, and Caroline T. Tiemessen*

MRC AIDS Virus Research Unit, National Institute for Virology, and Department of Virology, University of the Witwatersrand, Johannesburg, South Africa

Received 29 June 1998/Returned for modification 25 August 1998/Accepted 20 November 1998

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 < 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 < 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 < 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 < 0.01) and IL-8RB-expressing (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 intensity, 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 may have important implications for antimicrobial defenses and for normal immune processes.


* Corresponding author. Mailing address: National Institute for Virology, Private Bag X4, Sandringham 2131, South Africa. Phone: (01027-11) 321-4200/85. Fax: (01027-11) 882-0596. E-mail: caroline{at}niv.ac.za.


Infection and Immunity, March 1999, p. 1251-1260, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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