Effects on the Immune System 3993
Cannabinoids and Infections
3.1
In Vitro Infections
A variety of mammalian cellular systems have been used as experimental models
for documenting the in vitro effects of cannabinoids on immune responsiveness
to viruses, bacteria, and amoebae. Blevins and Dumic (1980) indicated that THC
had a protective effect against HSV infection in vitro.It was found that both HSV-
1 and HSV-2 failed to replicate and produce extensive cytopathic effect (c.p.e.)
in human cell monolayer cultures exposed before infection, at infection, or post
infection to various concentrations of THC. In contrast, other studies indicate that
THC compromises resistance to virus infection. It has been reported that THC
inhibits macrophage extrinsic anti-viral activity (Cabral and Vásquez 1991; Cabral
and Vásquez 1992) whereby macrophages normally suppress virus replication in
cells to which they attach (Morahan et al. 1980; Stohlman et al. 1982). Noe et al.
(1998) reported that a variety of cannabinoid receptor agonists enhanced syncytia
formation in human T cell leukemia virus-I (HTLV-I)-transformed human T (MT-
2)cellsinfectedwithcellfreehumanimmunodeficiencyvirus(HIV-1MN).It
was found that CP 55,940, THC, WIN 55,212-2, and WIN 55,212-3 significantly
increased syncytia formation, a phenomenon that has been reported to serve as
an indicator of HIV infection and cytopathicity.
In addition to exerting modulatory effects on virus replication, cannabinoids
have been reported to affect macrophage interaction with bacteria. Arata and
colleagues (Arata et al. 1991, 1992) reported that THC could overcome the re-
striction of the growth ofLegionella pneumophila, a facultative intracellular
pathogen that replicates readily in human and guinea pig macrophages and in
peritoneal exudate macrophages from A/J mice. Pretreatment of macrophages
with THC did not affect ingestion or replication ofLegionella. However, treatment
with THC following infection withLegionellaresulted in increased numbers of
intracellular bacteria. Stimulation of macrophages with LPS resulted in a reduc-
tion inLegionellagrowth within macrophages. In contrast, treatment of these
LPS-activated macrophages with THC resulted in greater growth ofLegionella,
indicating that the drug abolished the LPS-induced enhanced resistance. Gross
et al. (2000) suggested a role for the CB 1 receptor in THC-mediated ablation of
infection of macrophages by the intracellular pathogenBrucella suis, a gram-
negative bacterium. Multiplication ofBrucellawithin macrophages was inhibited
by the CB 1 antagonist SR141716A but not by the CB 2 antagonist SR144528. THC
has been shown also to alter the capacity of macrophages in vitro to killNaegleria
fowleri (Burnette-Curley et al. 1993), free-living amoebae that can cause a fa-
tal disease in humans known as primary amoebic meningoencephalitis (PAME)
(Marciano-Cabral 1988).