Smoking and nicotine exposure delay development of collagen-induced arthritis in mice.
BACKGROUND
Recent epidemiologic studies have implicated smoking as an environmental risk factor for the development of rheumatoid arthritis (RA). The aim of the present study is the evaluation of the role of cigarette smoke (CS) in the pathogenesis of collagen-induced arthritis in mice.


METHODS
DBA/1 mice exposed to CS for 16 weeks (n = 25) and mice exposed to nicotine in drinking water (n = 10) were immunized with collagen type II (CII). Severity of arthritis was evaluated clinically and morphologically and compared with control mice (n = 35). Intensity of inflammation was evaluated by serum IL-6 and TNF-alpha levels. Additionally, antibody response to CII (anti-CII) and citrullinated peptides (aCCP) was measured.


RESULTS
Clinical evaluation of arthritis showed a delayed onset of arthritis in CS-exposed mice compared with non-smoking controls (P < 0.05). Histologic index and weight changes were comparable between the groups; however, smoking mice presented less weight loss during the acute phase of the disease and gained weight significantly faster in the recovery phase (P < 0.05). Similar results were obtained in the mice exposed to nicotine. Nicotine also showed a direct anti-inflammatory effect diminishing IL-6 production by stimulated splenocytes in vitro (P < 0.001). Additionally, smoking mice had lower levels of aCCP and anti-CII antibodies compared with non-smoking (P < 0.05).


CONCLUSIONS
Neither smoking nor nicotine exposure aggravates development of CII-induced arthritis in mouse model. Moreover, CS exposure was associated with a lower level of anti-CII antibodies, providing a possible explanation for a delay of arthritis onset in this group.
Lindblad
Sofia S
SS
Department of Rheumatology and Inflammation Research, University of Gothenburg, Sahlgrenska University Hospital, Guldhedsgatan 10, Göteborg S-41346, Sweden. sofia.lindblad@rheuma.gu.se
Mydel
Piotr
P
Jonsson
Ing-Marie
IM
Senior
Robert M
RM
Tarkowski
Andrej
A
Bokarewa
Maria
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D002645:Chickens; D018450:Disease Progression; D024022:Fibrillar Collagens / Q000627:therapeutic use* / Q000633:toxicity; D018836:Inflammation Mediators / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009538:Nicotine / Q000627:therapeutic use*; D012907:Smoking / Q000473:pathology; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D024022:Fibrillar Collagens; D018836:Inflammation Mediators; D009538:Nicotine