Abstract
Topical microbicides are intended for frequent use by women in reproductive age. Hence, it is essential to evaluate their impact on mucosal immune function in the vagina. In the present study, we evaluated nisin, a naturally occurring antimicrobial peptide (AMP), for its efficacy as an intravaginal microbicide. Its effect on the vaginal immune function was determined by localizing Toll-like receptors (TLRs-3, 9) and cytokines (IL-4, 6 , 10 and TNF-α) in the rabbit cervicovaginal epithelium following intravaginal administration of high dose of nisin gel for 14 consecutive days. The results revealed no alteration in the expression of TLRs and cytokines at both protein and mRNA levels. However, in SDS gel-treated group, the levels were significantly upregulated with the induction of NF-κB signalling cascade. Thus, TLRs and cytokines appear as sensitive indicators for screening immunotoxic potential of candidate microbicides.
Highlights
Topical microbicides are being sought for preventing the transmission of human immunodeficiency virus (HIV) infection and other sexually transmitted infections (STIs) [1]
The success of anti-HIV/STI microbicides depends on their ability to maintain natural vaginal defenses, since the stratified epithelium of human vagina in unison with the microflora provides an efficient barrier against HIV1 [2]
It is known that inflammatory conditions induced by pathogens or chemical irritants may lead to a higher risk of acquiring and transmitting HIV-1 due to epithelial disruption and recruitment of HIV-1 by immune cells [3]
Summary
Topical microbicides are being sought for preventing the transmission of human immunodeficiency virus (HIV) infection and other sexually transmitted infections (STIs) [1]. It is known that inflammatory conditions induced by pathogens or chemical irritants may lead to a higher risk of acquiring and transmitting HIV-1 due to epithelial disruption and recruitment of HIV-1 by immune cells [3]. During early efforts to develop safe and effective topical microbicides to eliminate the risk of sexual transmission of STIs/HIV-1, Nonoxynol-9 (N-9), a chemical-based product, emerged as the lead candidate due to its potent activity against microbes in vitro and widespread commercial use as a contraceptive [4, 5]. Cellulose sulfate (6%) and carraguard failed as microbicides despite preclinical safety trials (http://www.aidsmap.com)
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