Low level light effects on inflammatory cytokine production by rheumatoid arthritis synoviocytes.

BACKGROUND AND OBJECTIVE: Low level light therapy (LLLT) is being evaluated for treating chronic and acute pain associated with rheumatoid arthritis (RA) and other inflammatory diseases. The mechanisms underlying the effectiveness of LLLT for pain relief in RA are not clear. The objectives of this study were to determine whether LLLT decreased production of pro-inflammatory cytokines by cells from RA joints, and, if so, to identify cellular mechanisms. STUDY DESIGN/MATERIALS AND METHODS: Synoviocytes from RA patients were treated with 810 nm radiation before or after addition of tumor necrosis factor-alpha (TNF-alpha). mRNA for TNF-alpha, interleukin (IL)-1beta, IL-6, and IL-8 was measured after 30, 60, and 180 minutes using RT-PCR. Intracellular and extracellular protein levels for 12 cytokines/chemokines were measured at 4, 8, and 24 hours using multiplexed ELISA. NF-kappaB activation was detected using Western blotting to follow degradation of IkappaBalpha and nuclear localization of the p65 subunit of NF-kappaB. RESULTS: Radiation at 810 nm (5 J/cm(2)) given before or after TNF-alpha decreases the mRNA level of TNF-alpha and IL-1beta in RA synoviocytes. This treatment using 25 J/cm(2) also decreases the intracellular levels of TNF-alpha, IL-1beta, and IL-8 protein but did not affect the levels of seven other cytokines/chemokines. TNF-alpha-induced activation of NF-kappaB is not altered by 810 nm radiation using 25 J/cm(2). CONCLUSIONS: The mechanism for relieving joint pain in RA by LLLT may involve reducing the level of pro-inflammatory cytokines/chemokines produced by synoviocytes. This mechanism may be more general and underlie the beneficial effects of LLLT on other inflammatory conditions.

Low-level laser therapy for zymosan-induced arthritis in rats: Importance of illumination time.

BACKGROUND: It has been proposed for many years that low-level laser (or light) therapy (LLLT) can ameliorate the pain, swelling, and inflammation associated with various forms of arthritis. Light is thought to be absorbed by mitochondrial chromophores leading to an increase in adenosine triphosphate (ATP), reactive oxygen species and/or cyclic AMP production and consequent gene transcription via activation of transcription factors. However, despite many reports about the positive effects of LLLT in arthritis and in medicine in general, its use remains controversial. For all indications (including arthritis) the optimum optical parameters have been difficult to establish and so far are unknown. METHODS: We tested LLLT on rats that had zymosan injected into their knee joints to induce inflammatory arthritis. We compared illumination regimens consisting of a high and low fluence (3 and 30 J/cm(2)), delivered at high and low irradiance (5 and 50 mW/cm(2)) using 810-nm laser light daily for 5 days, with the positive control of conventional corticosteroid (dexamethasone) therapy. RESULTS: Illumination with 810-nm laser was highly effective (almost as good as dexamethasone) at reducing swelling and a longer illumination time (10 or 100 minutes compared to 1 minute) was more important in determining effectiveness than either the total fluence delivered or the irradiance. LLLT induced reduction of joint swelling correlated with reduction in the inflammatory marker serum prostaglandin E2 (PGE2). CONCLUSION: LLLT with 810-nm laser is highly effective in treating inflammatory arthritis in this model. Longer illumination times were more effective than short times regardless of total fluence or irradiance. These data will be of value in designing clinical trials of LLLT for various arthritides.