Fatemeh Rajabian - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Zahra Tayarani-najaran - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Fatemeh Kalalinia - Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Objective: Cadmium (Cd) is a heavy and toxic metal. Cigarettes are an important source of Cd. Tobacco leaves absorb and concentrate high amounts of Cd from soil, water, fertilizer or pesticides. So smoking is the main cause of exposure to this metal. Cd has long half-life (7/4-7/9 year) and slow liberation from the body, as a result, Cd accumulates in the body. It has been reported that serum Cd levels are three times higher in smokers compared with non-smoker people. The cigarette smoking affects both the innate and adaptive immune systems. Cigarette smoking has emerged as an important risk factor for rheumatoid arthritis (RA). RA is a common autoimmune inflammatory disease with an estimated global prevalence of 0.3–1 %. In RA, synovitis occurs due to the influx of immune cells into the joints. T cells, along with B cells and other cells, produce pro-inflammatory cytokines and activated fibroblast-like synoviocytes, finally causing bone and cartilage damage.Methods: A literature search was conducted in scientific databases including PubMed, Scopus, Web of Science and Google Scholar. We used articles that were published until Juley 2019 to find studies that evaluated Cd toxicity on induction RA. The search included the following keywords: cadmium , cigarette , rheumatoid arthritis , cytokine , and autoimmune disorder . Results: Cd is associated with the production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNFα), Interleukin 1 (IL-1), IL-6, IL-8, decrease in the levels of anti-inflammatory cytokines such as IL-10 and to induce arthritis.Conclusion: Cadmium is present in large quantities in inhaled cigarette smoke. The inhalation of cadmium is a significant trigger factor for seropositive RA development in cigarette users. Cd is responsive to the elevation of pro-inflammatory cytokines also the degradation of anti-inflammatory cytokine and cigarette smokers suffer from RA two times more than non-smokers.

Cadmium, cigarette, rheumatoid arthritis, cytokine, autoimmune disorder