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Antimicrob. Agents Chemother. doi:10.1128/AAC.00250-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Cytokine expression in the colonic mucosa of HIV-infected individuals before and during nine months of antiretroviral therapy

Medizinische Klinik I, Charité, Campus Benjamin Franklin, 12200 Berlin, Germany; Abteilung für Infektiologie, Vivantes Auguste-Viktoria Klinikum, Rubensstraße 125, 12157 Berlin; Ärzteforum Seestraße, 13347 Berlin, Germany; Institut für Pathologie, Charité, Campus Benjamin Franklin, 12200 Berlin, Germany; Institut für Virology, Charité, Campus Benjamin Franklin, 12203 Berlin, Germany

^* To whom correspondence should be addressed. Email: hartmut_s{at}gmx.at.

	Abstract

Background: High-level HIV replication and the rapid breakdown of the mucosal immune system are the hallmarks of HIV infection in the gut. Cytokine dysregulation may be related to both phenomena.

Methods: Using real-time PCR we quantified the colonic mucosal mRNA expression of selected proinflammatory/regulatory (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-10) and HIV-inhibitory (IL-16, CCL3, CCL5) cytokines in 10 HIV-infected patients before and during nine months of highly active antiretroviral therapy. HIV RNA and T-cell dynamics were measured in the colonic mucosa and the blood. Seven HIV(-) individuals served as controls.

Results: The mucosal mRNA expression of TNF-alpha, IFN-gamma, IL-4, IL-6 and IL-10 was significantly higher in HIV-infected patients as compared to controls and remained elevated during nine months of HAART despite the decline of blood and mucosal HIV RNA and a rise of CD4(+) T-lymphocytes. The mRNA levels of CCL3 and CCL5, both elevated before treatment, returned to near normal during therapy.

Discussion: Despite reductions of mucosal HIV RNA and the repletion of mucosal CD4(+) T-lymphocytes, antiretroviral therapy fails to restore the normal colonic immunologic environment.