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CVI Accepts, published online ahead of print on 31 October 2007
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Clin. Vaccine Immunol. doi:10.1128/CVI.00216-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Correlates of Cytokine Protein Levels in Cervical Mucus Samples in Young Women by a Multiplex Immunoassay Method

Jay A. Lieberman, Anna-Barbara Moscicki, Jan L. Sumerel, Yifei Ma, and Mark E. Scott*

Division of Adolescent Medicine, Department of Pediatrics, University of California, San Francisco, California, 94143 and BioSource International, Camarillo, California, 93012

* To whom correspondence should be addressed. Email: scottm{at}peds.ucsf.edu.


   Abstract

Background. Cytokines in cervical mucus are likely to play important roles in controlling pathogens. The cervical mucosal environment is complex, however, with many endogenous and exogenous factors that may affect cytokine levels.

Methods. We used a multiplex, suspension–array-based immunoassay method to measure 10 proinflammatory (interleukin [IL]-1{beta}, IL-6, and IL-8) and immunoregulatory (gamma interferon [IFN-{gamma}], IL-2, IL-4, IL-5, IL-10, IL-12, and IL-13) cytokines in cervical mucus specimens—collected via ophthalmic sponge from 72 healthy, non-pregnant women—and correlate their levels with biologic and behavioral covariates in a cross-sectional design.

Results. Proinflammatory and immunoregulatory cytokines were readily detected, although the former were present at markedly higher levels than the latter. Among covariates examined, the most striking finding was the significant (p=0.05) association between depressed levels of the cytokines IFN-{gamma}, IL-1{beta}, IL-6, and IL-10 and cigarette smoking. Also, non-significant trends toward lower cytokine levels were found in the settings of incident and persistent human papillomavirus infection.

Conclusions. The ready detection of proinflammatory cytokines may be reflective of the female genital tract as an anatomical site that is constantly exposed to immunogenic stimulation. Cigarette smoking appears to downregulate cytokine responses in the cervical mucosa, which may help explain the implicated role of tobacco use as a cofactor for cervical cancer development.







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