Associations of cytokine concentrations with key osteopathic lesions and clinical outcomes in patients with nonspecific chronic low back pain: Results from the osteopathic trial

Context: Little is known about the role that cytokines play in osteopathic manual treatment (OMT) of patients with chronic low back pain (LBP). Objective: To measure the baseline concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in patients with chronic LBP; the correlations of these cytokine concentrations with clinical measures, including the number of key osteopathic lesions; the changes in cytokine concentrations with OMT; and the association of such changes with clinical outcomes. Design: Substudy nested within a randomized controlled trial of OMT for nonspecific chronic LBP. Setting: University-based study in Dallas-Fort Worth, Texas. Patients: Seventy adult research patients with nonspecific chronic LBP. Main Outcome Measures: A 10-cm visual analog scale, the Roland-Morris Disability Questionnaire, and the Medical Outcomes Study Short Form-36 Health Survey were used to measure LBP severity, back-specific functioning, and general health, respectively. Results: At baseline, IL-1β (ρ=0.33; P=.005) and IL-6 (ρ=0.32; P=.006) were each correlated with the number of key osteopathic lesions; however, only IL-6 was correlated with LBP severity (ρ=0.28; P=.02). There was a significantly greater reduction of TNF-α concentration after 12 weeks in patients who received OMT compared with patients who received sham OMT (Mann-Whitney U=251.5; P=.03). Significant associations were found between OMT and a reduced TNF-α concentration response at week 12 among patients who achieved moderate (response ratio, 2.13; 95% confidence interval [CI], 1.11-4.06; P=.006) and substantial (response ratio, 2.13; 95% CI, 1.07-4.25; P=.01) LBP improvements, and improvement in back specific functioning (response ratio, 1.68; 95% CI, 1.04-2.71; P=.03). Conclusions: This study found associations between IL-1β and IL-6 concentrations and the number of key osteopathic lesions and between IL-6 and LBP severity at baseline. However, only TNF-α concentration changed significantly after 12 weeks in response to OMT. These discordant findings indicate that additional research is needed to elucidate the underlying mechanisms of action of OMT in patients with nonspecific chronic LBP. Main Outcome Measures: A 10-cm visual analog scale, the Roland-Morris Disability Questionnaire, and the Medical Outcomes Study Short Form-36 Health Survey were used to measure LBP severity, back-specific functioning, and general health, respectively. Results:At baseline, IL-1β (?=0.33; P=.005) and IL-6 (?=0.32; P=.006) were each correlated with the number of key osteopathic lesions; however, only IL-6 was correlated with LBP severity (?=0.28; P=.02). There was a significantly greater reduction of TNF-α concentration after 12 weeks in patients who received OMT compared with patients who received sham OMT (Mann-Whitney U=251.5; P=.03). Significant associations were found between OMT and a reduced TNF-α concentration response at week 12 among patients who achieved moderate (response ratio, 2.13; 95% confidence interval [CI], 1.11-4.06; P=.006) and substantial (response ratio, 2.13; 95% CI, 1.07-4.25; P=.01) LBP improvements, and improvement in back-specific functioning (response ratio, 1.68; 95% CI, 1.04-2.71; P=.03). Conclusions: This study found associations between IL-1β and IL-6 concentrations and the number of key osteopathic lesions and between IL-6 and LBP severity at baseline. However, only TNF-α concentration changed significantly after 12 weeks in response to OMT. These discordant findings indicate that additional research is needed to elucidate the underlying mechanisms of action of OMT in patients with nonspecific chronic LBP.