Nicotine Inhibits Clostridium difficile Toxin A-Induced Colitis but Not Ileitis in Rats

Figure 1

Dose-response effects of nicotine on toxin A-induced (5 μg) colonic luminal fluid accumulation (a), MPO content (b), and histopathology (c–j). Toxin A strongly and significantly stimulates colonic luminal fluid accumulation and MPO activity. Nicotine has a biphasic effect on these actions of toxin A. At low doses, nicotine dose-dependently inhibited these effects of toxin A. At higher doses, nicotine inhibited toxin A colitis progressively less but never increased inflammation beyond the effect of toxin A alone. versus control; versus toxin A; . (c) Control section illustrating the normal histology of the rat colon. (d) Nicotine (0.2 μg) alone has no effect on colonic histology. (e) Toxin A (5 μg) causes extensive inflammatory damage to the colon including loss of mucosal folding, distortion of crypts, surface ulceration, and influx of inflammatory cells including neutrophils. (f) Toxin A (5 μg) after pretreatment with 0.002 μg nicotine. This dose of nicotine had little effect on toxin A colitis. (g) Toxin A (5 μg) after pretreatment with 0.02 μg nicotine. This dose of nicotine had little effect on toxin A colitis. (h) Toxin A (5 μg) after pretreatment with 0.2 μg nicotine. This dose of nicotine appeared to protect almost completely against toxin A colitis. (i) Toxin A (5 μg) after pretreatment with 2 μg nicotine. This dose of nicotine had little effect on toxin A colitis. (j) Toxin A (5 μg) after pretreatment with 20 μg nicotine. This dose of nicotine had little effect on toxin A colitis. These results agree well with the effects of nicotine on toxin A-induced luminal fluid accumulation and MPO activity shown in (a) and (b). Line bar = 100 μm.

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