Ca. Newton et al., SECONDARY IMMUNITY TO LEGIONELLA-PNEUMOPHILA AND TH1 ACTIVITY ARE SUPPRESSED BY DELTA-9-TETRAHYDROCANNABINOL INJECTION, Infection and immunity, 62(9), 1994, pp. 4015-4020
Resistance to infection with Legionella pneumophila is primarily depen
dent upon cell mediated immunity rather than humoral immunity. Recent
evidence suggests that activation of cell-mediated immunity depends on
Th1 cells and activation of humoral immunity depends on Th2 cells. In
this report, Delta(9)-tetrahydrocannabinol (THC), the major psychoact
ive cannabinoid of marijuana and an immunomodulator, suppressed develo
pment of secondary immunity to L. pneumophila, which correlated,vith a
reduction in Th1 activity. BALB/c mice, infected with a primary suble
thal dose of L. pneumophila, developed resistance to a larger challeng
e infection 3 to 4 weeks later. However, intravenous injection of THC
(4 mg/kg of body weight) 1 day prior to primary infection resulted in
increased mortality after the challenge infection. The level of anti-L
, pneumophila antibodies in serum increased in both THC-treated and co
ntrol mice; however, in the THC group IgG1 antibodies which are stimul
ated by Th2 cells were elevated while Th1-regulated, IgG2a antibodies
were depressed. Furthermore, cultured splenocytes from THC-treated mic
e had less L. pneumophila-specific lymphoproliferation, indicating a d
eficiency in cell-mediated immunity. Normal mouse splenocytes treated
in vitro with THC and pokeweed mitogen showed suppressed production of
gamma interferon, a cytokine associated with Th1 cells, but increased
production of interleukin 4, a cytokine produced by Th2 cells. Spleno
cytes from THC-treated mice, stimulated in vitro with either pokeweed
mitogen or anti-CD3 antibodies, also produced less gamma interferon, i
ndicating less Th1 activity in these mice. These results suggest that
THC decreases the development of anti-L. pneumophila immunity by causi
ng a change in the balance of Th1 and Th2 activities.