Endotoxin and Cancer

Abstract

ObjectiveExposure to endotoxin, a component of gram-negative bacterial cell walls, is widespread in many industrial settings and in the ambient environment. Heavy-exposure environments include livestock farms, cotton textile facilities, and saw mills. Concentrations are highly variable in non-occupational indoor and outdoor environments. Endotoxin is a potent inflammagen with recognized health effects, including fever, shaking chills, septic shock, toxic pneumonitis, and respiratory symptoms. Somewhat paradoxically, given the putative role of inflammation in carcinogenesis, various lines of evidence suggest that endotoxin may prevent cancer initiation or limit tumor growth. The hypothesis that components of bacteria may retard cancer progression dates back to William B. Coley’s therapeutic experiments (“bacterial vaccine”) in the 1890s.Data sourcesIn this article, we review epidemiologic, clinical trial, and experimental studies pertinent to the hypothesis that endotoxin prevents cancer. Since the 1970s, epidemiologic studies of cotton textile and other endotoxin-exposed occupational groups have consistently demonstrated reduced lung cancer risks. Experimental animal toxicology research and some limited therapeutic trials in cancer patients offer additional support for an anticarcinogenic potential. The underlying biological mechanisms of anticarcinogenesis are not entirely understood but are thought to involve the recruitment and activation of immune cells and proinflammatory mediators (e.g., tumor necrosis factor α and interleukin-1 and -6).ConclusionsIn view of the current state of knowledge, it would be premature to recommend endotoxin as a cancer-chemopreventive agent. Nonetheless, further epidemiologic and experimental investigations that can clarify further dose–effect and exposure–timing relations could have substantial public health and basic biomedical benefits.

Infection and Cancer: Revaluation of the Hygiene Hypothesis

“…26,27) or microbial products [e.g., lipopolysaccharide (LPS); refs. 28,29] can exhibit both pro-and anticarcinogenic functions and, therefore, many questions remain unresolved.…”

“…There is also evidence of the antitumor effect of certain microbial products (e.g., LPS) and attenuated pathogen forms [e.g., Bacillus Calmette-Gu erin (BCG) vaccine; refs. 13,28,55]; more specifically, BCG, vaccinia, or yellow fever virus vaccinations have been linked to melanoma protection (56,57). In addition, infectious agents have also been inversely associated with cancer (Table 1), as in the case of Trypanosoma cruzi, which can result in lower incidence of experimentally induced rodent colon cancer (58).…”

IFNβ Produced by TLR4-Activated Tumor Cells Is Involved in Improving the Antitumoral Immune Response

“…Recently, functional TLRs were found to be expressed in cancer cells, but their significance remains controversial (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Whereas most of the therapeutic strategies using microbial products were designed with the idea of activating TLRs present on innate immune system cells (3)(4)(5)(6)(7)(8)(9)(10), clear distinction about the separate contribution of immune and cancer cells to the immune response has yet to be done. Stimulation of TLR4, the main receptor of bacterial lipopolysaccharide (LPS), on tumor cells has been shown to have a positive role in tumorigenesis in in vivo (13)(14)(15), but mainly in in vitro settings (16)(17)(18)(19).…”

Natūralus imunitetas atavistiniam endotoksinui eksperimentinėje onkologijoje ir žmogaus vėžio profilaktikoje (naujos koncepcijos apžvalga)

“…Jis prasiskverbia į organizmą. Mažesnis mirtingumas yra aiškinamas endotoksino apsauginiais mechanizmais aktyvinant imuninius procesus [26][27][28][29][30].…”

“…Atavistinio endotoksino patogenetinį ryšį su navikinio proceso formavimosi mechanizmais parodo ir jau minėti epidemiologiniai darbai su egzogeniu endotoksinu, esančiu medvilnės ir lino pramonės darbininkų ir žemės ūkio darbuotojų aplinkoje [26][27][28][29][30]. Fenomenas, kad žmogaus aplinkoje esantis endotoksinas, patekęs į organizmą, mažina riziką susirgti vėžiu, patvirtina mūsų apibendrinimą apie IgMNAE įtaką onkologinių ligų mažėjimui ir nurodo būtinumą stiprinti žmonių populiacijos natūralų imunitetą atavistiniam endotoksinui.…”