Spinal Manipulative Therapy Reduces Inflammatory Cytokines but Not Substance P Production in Normal Subjects

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:   Frankp@chiro.org

FROM:   J Manipulative Physiol Ther 2006 (Jan);   29 (1):   14–21

Julita A. Teodorczyk-Injeyan, PhD, H. Stephen Injeyan, PhD, DC, Richard Ruegg, PhD, DC

Division of Research, Canadian Memorial Chiropractic College, Toronto, Ontario, Canada. This study was supported by the Canadian Memorial Chiropractic College and a Public Health Service grant no. U24 AR45166 through the Consortial Center for Chiropractic Research.


OBJECTIVE:   To examine the effect of a single spinal manipulation therapy (SMT) on the in vitro production of inflammatory cytokines, tumor necrosis factor alpha, and interleukin (IL) 1beta, in relation to the systemic (in vivo) levels of neurotransmitter substance P (SP).

METHODS:   Sixty-four asymptomatic subjects were assigned to SMT, sham manipulation, or venipuncture control group. SMT subjects received a single adjustment in the thoracic spine. Blood and serum samples were obtained from subjects before and then at 20 minutes and 2 hours after intervention. Whole-blood cultures were activated with lipopolysaccharide (LPS) for 24 hours. Cytokine production in culture supernatants and serum SP levels were assessed by specific immunoassays.

RESULTS:   Over the study period, a significant proportion (P ≤ .05) of sham and control subjects demonstrated progressive increases in the synthesis of tumor necrosis factor alpha and IL-1beta. Conversely, in a comparable proportion of cultures from SMT-derived subjects, the production of both cytokines decreased gradually. Normalization of the observed alterations to reflect the changes relative to self-baselines demonstrated that, within 2 hours after intervention, the production of both cytokines increased significantly (P < .001 to .05) in both controls. In contrast, a significant (P < .001 to .05) reduction of proinflammatory cytokine secretion was observed in cultures from SMT-receiving subjects. In all study groups, serum levels of SP remained unaltered within 2 hours after intervention.

DISCUSSION:   The present study supports the hypothesis that the spinovisceral reflex effect can encompass functional activity of the immune system. We believe this to be the first report to demonstrate that a single manipulative thrust to an aberrant vertebral motion segment in the upper thoracic spine of asymptomatic subjects results in down-regulation of the capacity of human leukocytes for the production of proinflammatory cytokines induced by LPS. The study design used in the present report allowed us to create a model in which the LPS-induced inflammatory response in vitro, in control subjects submitted to multiple venipunctures, became augmented. The progressive augmentation of the production of both TNF-a and IL-1ß observed in cell preparations from VC and SHM subjects was not unexpected. It has been shown that even minor surgical intervention and local blood clotting may lead to increased expression of messenger RNA for inflammatory cytokines such as TNF-a and IL-6 and thereby result in increased secretion of both cytokines.17 Furthermore, immunological and inflammatory changes may be induced by a number of factors such as crush, cut, contusion, biopsy, or stress, and the biologic function of circulating blood cells can be altered by the impact of events in local tissues.18,19 Several of these factors, without doubt, contributed to increased levels of constitutive secretion of TNF in LPS-free controls. Interestingly, such increases were not observed in SMT-treated subjects. The SMT group was exposed to the same number of venipuncture procedures as the control groups. Thus, attenuation of TNF-a and IL-1ß in cultures from SMT-receiving normal subjects suggests that spinal manipulation effectively ameliorated the subsequent physiological responses of the peripheral blood cells to inflammatory stimuli.

Recent clinical studies have shown that TNF-a blockade by anti–TNF-a monoclonal antibodies was highly effective in reducing sciatic pain.37 Based on these and related results, development of drugs targeting the production and/or action of proinflammatory cytokines is now suggested as critical for pain management in patients with low back pain and sciatica.38 In contrast to pharmacological interventions, SMT is likely to present a noninvasive and efficacious alternative to such therapies. Future studies are now necessary to address the issue of the effect of SMT on the magnitude and duration of inflammatory responses in chiropractic patients.

CONCLUSIONS:   SMT-treated subjects show a time-dependent attenuation of LPS-induced production of the inflammatory cytokines unrelated to systemic levels of SP. This suggests SMT-related down-regulation of inflammatory-type responses via a central yet unknown mechanism.

This work was originally funded by the   Consortial Center of Chiropractic Research (CCCR)

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