Photomedicine and Laser Surgery Volume 26, Number 1, 2008 © Mary Ann Liebert, Inc. Pp. 19–24 DOI: 10.1089/pho.2007.2119 Cytokine mRNA Expression Is Decreased in the Subplantar Muscle of Rat Paw Subjected to Carrageenan-Induced Inflammation after Low-Level Laser Therapy REGIANE ALBERTINI, Ph.D., 1 ANTONIO BALBIN VILLAVERDE, Ph.D., 1 FLAVIO AIMBIRE, Ph.D., 1 JAN BJORDAL, Ph.D., 2,3 ALDO BRUGNERA JR., Ph.D., 4 JOSANE MITTMANN, Ph.D., 1 JOSE ANTONIO SILVA JR., Ph.D., 5 and MARICILIA COSTA, Ph.D. 1 ABSTRACT Objective: The objective of this work was to investigate the anti-inflammatory effects of low-level laser ther- apy, applied at different wavelengths (660 and 684 nm), on cytokine mRNA expression after carrageenan-in- duced acute inflammation in rat paw. Background Data: Low-level laser therapy (LLLT) has been observed to reduce pain in inflammatory disorders. However, little is known about the mechanisms behind this effect or whether it is wavelength-specific. Materials and Methods: The test sample consisted of 32 rats divided into four groups: A 1 (control-saline), A 2 (carrageenan-only), A 3 (carrageenan + 660 nm laser therapy), and A 4 (carrageenan  684 nm laser therapy). The animals from groups A 3 and A 4 were irradiated 1 h after induc- tion of inflammation by carrageenan injection. Continuous-wave red lasers with wavelengths of 660 and 684 nm and dose of 7.5 J/cm 2 were used. Results: Both the 660 nm and 684 nm laser groups had 30%–40% lower mRNA expression for cytokines TNF-, IL-1, and IL-6 in the paw muscle tissue than the carrageenan-only control group. Cytokine measurements were made 3 h after laser irradiation of the paw muscle, and all cy- tokine differences between the carrageenan-only control group and the LLLT groups were statistically sig- nificant (p  0.001). Conclusions: LLLT at the 660-nm and 684-nm wavelengths administered to inflamed rat paw tissue at a dose of 7.5 J/cm 2 reduce cytokine mRNA expression levels within 3 h in the laser-irradiated tissue. 19 INTRODUCTION P RO-INFLAMMATORY CYTOKINES such as tumor necrosis fac- tor- (TNF-) and the interleukins are important mediators of inflammation, immunity, proteolysis, and cell recruitment and proliferation. Over the past decade, TNF- and interleukin- 1 (IL-1) have received much attention in the literature, 1–3 and the contributions of both cytokines to the pathology of rheu- matoid arthritis (RA) have been demonstrated by several dif- ferent groups. 3,4 It has been shown that in the pathogenesis of RA, TNF- plays a pivotal role, especially on the regulation of IL-1 expression. 2,3 This regulation is important for the in- duction of matrix metalloproteinase and prostanoid production by sinovial fibroblasts and chondrocytes. 1,5 Cellular interac- tions mediated by TNF- and IL-1 have become prominent factors in numerous reviews proposing a sequence of events leading to cartilage damage in RA. 2,3,5 The precise factors inducing monocytes/macrophages to pro- duce both TNF- and IL-1 remain unknown. However, a pleiotropic action has been suggested for these cytokines. 6–8 They are reportedly expressed by activated monocytes, epithe- lial cells, and fibroblasts in inflammatory disorders. 9 Numer- ous biological effects have been attributed to both TNF- and IL-1, such as induction of proliferation of mitogen-activated T cells, contribution to B-cell proliferation and immunoglobu- lin (Ig) synthesis, and enhancement of neutrophil and natural 1 Instituto de Pesquisa and Desenvolvimento (IP&D), Universidade do Vale do Paraíba (UNIVAP), São José dos Campos, SP, Brazil, 2 Bergen University College, Physiotherapy Department, 3 Section of Physiotherapy Science, Institute of Health and Primary Health Care, University of Bergen, Bergen, Norway, 4 Dental Laser Center, Universidade do Vale do Paraíba (UNIVAP), and 5 Departamento de Ciências da Reabilitação, Centro Universitário Nove de Julho (UNINOVE), São Paulo, SP, Brazil.