Cannabinoid influence on cytokine profile in multiple sclerosis

Abstract

Cannabinoids have been suggested as possessing immunomodulatory properties, and cannabinoid receptors are present on leucocytes. Clinically, there is some evidence that cannabinoids may be therapeutically useful in treating multiple sclerosis, which is generally believed to be an autoimmune condition. This paper reports data derived from the Cannabinoids in MS (CAMS) study, which was the largest randomized controlled trial yet conducted to evaluate the therapeutic efficacy of cannabinoids. We found no evidence for cannabinoid influence on serum levels of interferon (IFN)-gamma, interleukin (IL)-10, IL-12 or C-reactive protein as measured using enzyme-linked immunosorbent assay (ELISA), in comparison to control values. Mitogenic stimulation experiments also failed to demonstrate any significant reduction in percentage of CD3+, IFN-gamma producing cells after exposure to cannabinoids in vivo, although numbers were small. Further work is needed to establish the functional significance of cannabinoid receptors on immune cells.

Fig. 1

Box-plot presentation of data from patients with primary progressive MS for change in interferon (IFN)-γ (a), interleukin (IL)-10 (b), IL-12 (c) and CRP (d). The asterisk represents an extreme value more than three interquartial ranges from the box hinges.

Fig. 2

Box-plot presentation of data from secondary progressive patients for change in interferon (IFN)-γ (a), interleukin (IL)-10 (b), IL-12 (c) and CRP (d). Asterisks represent extreme values more than three interquartial ranges from the box hinges; open circles represent outliers more than 15 interquartial ranges from the box hinges.

Fig. 3

Percentage of CD3 positive cells expressing interferon (IFN)-γ either pretreatment (pre) or during treatment (post) with 95% CI. CE = cannabis extract, THC = Δ⁹-THC, Plac = placebo).

Fig. 4

Flow cytometric profile of frequencies of CD3⁺ T cell producing interferon (IFN)-γ. Peripheral blood mononuclear cells (PBMC) were cultured with progressive multiple sclerosis (PMS), ionomycin and monensin for 7 h, fixed and permeabilized.