During orthodontic tooth movement (OTM), there is the release of cytokines in the gingival crevicular fluid (GCF) that are supposed to participate in the bone remodeling. This systematic review aimed at assessing the effects of photobiomodulation (PBM) on the levels of these cytokines during OTM. This systematic review according to Cochrane Collaboration guidelines aimed to answer the clinical question following the PICOS strategy. The broad search in the literature was performed before 05 April, 2021 in six electronic databases (Pubmed, Web of Science, Scopus, Embase, Cochrane, Biblioteca Virtual de Saude) and supplemented by the grey literature. The risk of bias of randomized and non-randomized clinical trials was evaluated by two tools: RoB 2 and ROBINS-I. Mean and standard deviation of cytokine levels was extracted to meta-analysis, and the GRADE system was applied to assess the quality of the evidence. Nine studies were included in this review. Low-level laser therapy (LLLT) was the photobiomodulation type used in most of the studies (n = 8). The wavelengths used varied from 618 to 980 nm and also differed concerning the light emission pattern. LLLT increased the levels of IL-1beta, IL-8, OPN, and PGE2, but not TNF-alpha1, TGF-beta1. The levels of IL6, RANKL, and OPG presented conflicting results. LLLT was statistically associated with an increase of IL-1beta levels (standard mean difference [SMD] = 1.99; 95% confidence interval = 0.66 to 3.33; p < 0.001) with low certainty of evidence. LLLT may increase the levels of IL-1beta and other cytokines; however, the results should be interpreted with caution due to protocol variations between studies, and the few studies added in the meta-analysis.
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