Antiinflammatory Effects of Cannabinoids

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The early experimental data involving marijuana cannabinoids and immunity suggested the drugs were immunosuppressive. For example, in 1974 it was reported that T cell responses to mitogens were suppressed in cultured peripheral blood mononu

Table 1. Cannabinoid-based drugs increase cytokines

Cannabinoid

Receptor

Model

Cytokine stimulus

Cytokines

Humans

2-AG

CB2

HL-60

2-AG

CXCL8, CCL2

CP55,940

CB2

HL-60

CP55, 940

TNF, CXCL8,

CCL2, CCL4

Marijuana

ND

Peripheral

PHA, ConA

IL-10, TGF-ß

smoking

blood mono-

cytes

Mice

WIN55, 212-

ND

Splenocytes

LPS, Propionibacte

IL-10

2 or HU-210

rium acnes

THC

ND

Splenocytes

Legionella pneumophila

TNF, IL-6

THC

ND

Peritoneal

LPS

IL-1 a, IL-1ß

macrophages

THC

ND

Splenocytes

Legionella pneumophila

IL-4

THC

ND

Splenocytes

Tumor model

IL-10, TGF-ß

References: (Klein et al. 1993; Zhu et al. 1994; Derocq et al. 2000; Klein et al. 2006; Smith et al. 2000; Zhu et al. 2000; Pacifici et al. 2003; Kishimoto et al. 2004).

References: (Klein et al. 1993; Zhu et al. 1994; Derocq et al. 2000; Klein et al. 2006; Smith et al. 2000; Zhu et al. 2000; Pacifici et al. 2003; Kishimoto et al. 2004).

clear cells (PBMCs) taken from chronic marijuana smokers (Nahas et al. 1974). Since then, cannabinoid-based drugs have been shown to suppress the function of T cells, B cells, macrophages, NK cells, and dendritic cells. The studies in this area have been numerous and in vivo and in vitro animal systems from humans to mice have been explored and extensively reviewed over the years (Cabral and Dove Pettit 1998; Klein et al. 1998, 2000a, 2003; Klein 2005; Klein and Cabral 2006). However, more recently, drug effects on the cytokine network have been focused on and in these reports the drugs have been shown to modulate cytokine production, suggesting their therapeutic potential for the management of chronic inflammatory diseases that are often due to a dysregulation of the cytokine network. Tables 1 and 2 are summaries of recent results from mouse and human studies showing that, depending on the system studied, cannabinoid-based drugs either increase or decrease various cytokines. From the tables, it is apparent that most studies show a decrease in proin-flammatory cytokines such as IL-1, IL-2, IL-6, IL-12, TNF, GM-CSF, and IFN-y production; however, increases in anti-inflammatory cytokines such as IL-4, IL-10, and TGF-p are also observed potentially contributing in some systems to an overall decrease in inflammatory tone. Based on these data, clinical trials have been initiated examining the safety and efficacy of these drugs in chronic inflammatory diseases.

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