Aspects of the role of mineral oil as immunological adjuvants in rheumatoid arthritis

Abstract: Environmental factors are likely contributing factors in the development of Rheumatoid Arthritis (RA), an autoimmune disease, for which etiologic factors are still poorly known. Mineral oils are efficient adjuvants which increase immunological responses and are used in animal immunization and for induction of different experimental autoimmune diseases including arthritis. The relationship between environmental exposure to mineral oil and the risk of developing RA is the subject of this thesis. Both animal experimental studies and human epidemiological studies were performed in order to investigate the possible role of mineral oils in the development of arthritis. A special emphasis was devoted to investigations of whether exposure to cosmetics containing mineral oils was associated with arthritis in a similar way as exposure to the mineral oils themselves. Experimental studies using the Dark Agouti rat (DA rat) showed that five of the eight tested common, commercial cosmetic products containing mineral oil induced arthritis in DA rats after immunisation in the skin. One cosmetic product, so called baby oil, also induced a mild transient arthritis after percutaneous exposure. Two types of epidemiological studies were performed to investigate the relationship between occupational exposure to mineral oil and the risk of developing RA. First, a register-based cohort study was used to compare the cumulative incidence of RA between individuals with different occupations. The study population comprised of subjects who in 1980 lived in one of 13 Swedish counties and were born 1905-1945, and stated the same occupation in the census of 1960 and 1970. The study population was followed concerning hospital care for RA in 1981-1983 by linkage to the Swedish Hospital Discharge Register. A small increased risk of RA was observed in farmers, upholsterers, lacquerers, concrete workers and hair-dressers and in several occupations such as toolmakers, machinery and engine repairmen. Many of these occupations are associated with exposure to organic solvents and mineral oil, and this register study triggered our interest in initiating a case-control study investigating the environmental risk factors for RA, including the risk confined by mineral oil exposure. The case-control study comprised 1419 incident RA cases and 1674 controls. Men occupationally exposed to mineral oil were observed to have an increased risk of developing RA (Relative risk (RR) = 1.3, 95% confidence interval (CI) = 1.0-1.7). Mineral oil exposure was associated with a particularly high risk of developing rheumatoid factor positive RA (RR =1.4, 95% CI =1.0-2.0) and anti-citrulline positive RA (anti-CCP+RA) (RR =1.6, 95% CI=1.1-2.2). The highest risk of developing anti- CCP+RA (RR=1.7, 95% CI=1.1-2.6) was observed after exposure to hydraulic oil. The number of women occupationally exposed to mineral oils was too few to allow meaningful analyses. Association between cosmetic usage and the risk of developing RA was also investigated in the casecontrol study. However, no increased risk through use of common skin care products such as body lotions and skin creams was observed. Conclusion This thesis demonstrates that environmental exposure to mineral oil by itself, as well as being a component of cosmetics, can induce experimental arthritis in rats with certain genetic characteristics, and that occupational exposure to mineral oils is associated with an increased risk of developing RA. Our epidemiological study gave no evidence that use of cosmetics containing mineral oils was associated with an increased risk for RA.