Phytol Suppresses Established Arthritis

<div><p>(A) Phytol injection ameliorates acute arthritis. Therapeutic effect of phytol in acute phase of PIA in DA.<i>Ncf1</i>^DA rats after two injections (200 μl) 5 d apart (arrows) starting at the estimated peak of disease (day 22). (Significance indications above line represent SC administration and below IP administration) (control <i>n</i> = 18, IP <i>n</i> = 17, and SC <i>n</i> = 16).</p> <p>(B) Cartilage destruction is decreased after phytol injection. Plasma were taken day 38 and analyzed for COMP levels as a measurement of cartilage destruction. Results are presented as circles, where each circle represents one individual and filled circles represent rats with a mean reduction in score after day of first treatment (day 22). Lines represent mean values.</p> <p>(C) Phytol decreases arthritis severity in the chronic phase of arthritis. Phytol was injected IP twice (200 μl) (arrows), starting day 70 after pristane injection in DA.<i>Ncf1</i>^DA rats with 3 d between treatments (control, <i>n</i> = 19; phytol, <i>n</i> = 18).</p> <p>(D) Phytol affects macroscopic and microscopic inflammation. Pristane-injected rats treated with phytol on either day 0 or day 13 (<i>n</i> = 4). On day 22 rats were sacrificed and paws taken for histology and stained with erythrosine-hematoxylin (photomicrographs to right of graph; 20× magnification).</p> <p>(E) The preventive effect of phytol is not dependent on genetic background. Arthritis-preventing effect of phytol when injected (200 μl SC) 5 d before induction of PIA in LEW.1F rats (<i>n</i> = 9).</p> <p>(F) Phytol has an arthritis-ameliorating effect in rats that have a functional oxidative burst. Rats heterozygous for the functional <i>Ncf1</i> (<i>Ncf1</i>^E3) allele with an arthritis susceptibility locus on Chromosome 6 were injected IP (200 μl) with phytol at the estimated peak of disease (day 24, arrow; control, <i>n</i> = 13; phytol, <i>n</i> = 15).</p> <p>(G) Histamine dihydrochloride reverses the ameliorating effect of phytol, possibly by blocking oxidative burst. Injection of histamine twice (200 μl SC and IP), with 5 d between injections (arrows), starting 10 d after phytol treatment (day 26 after pristane) in DA.<i>Ncf1</i>^DA rats could reverse the arthritis-ameliorating effect (<i>n</i> = 5). Results are presented as difference in score compared to day of treatment (day 0).</p> <p>*<i>p</i> < 0.05, **<i>p</i> < 0.01, ***<i>p</i> < 0.001.</p>