S.Moretti

Doctorate School in Pharmacology 
Dept. of , Pharmacology, Chemiotherapy and Medical Toxicology ,  University of Milan, Italy 
 

Cannabis use has characteristics of very early onset, from 12 years of age and it is known that more than 25% of teens have used that substance during their life.
Among the many consequences related to the use of cannabis it has been recently  shown that  THC, as well as endogenous cannabinoids,  can affect  immune system functions. Recent studies proved that THC  decreases the resistance to bacterial and viral infections.The main objective of this study is to investigate whether the use of cannabis in adolescence   would cause  effects on the immune system that can last overtime ,and have an impact on susceptibility to infections, allergies and autoimmune disease  also in adulthood.
As immune parameters , we took into account both the innate and the acquired  immunity, measuring the production of cytokines  by T cells or macrophages. In this study we used Balb C / J male mice 20 -22 days  of age, which corresponds to human adolescences, and 80 day old mice as adults.
THC was administered at a dose of 25 mg / kg(s.c.)in repeated dosing for 10 days; control mice of the same age  were treated with vehicle alone for the same period.
Some groups of animals were sacrificed for immune measurements immediately after the end of the treatment, while other groups were left undisturbed until adulthood ( 80 days ) when  the immunological assessments were performed.
To study lymphocyte cytokines  ,young and adult animals were immunized with the protein KLH to induce an  antigen-specific reaction, similar to that obtained with the vaccination procedures in humans.
We evaluated immune parameters representative of the Th1 / Th2 cytokines balance, such as production of Th1 IL2 and IFNγ,andTh2IL4 bysplenocytes, as well as anti-KLH IgM production.
IgM and cytokine production was assessed using ELISA.
 To assess macrophage function  we used peritoneal macrophages stimulated in vitro with LPS.
The cytokines studied were the proinflammatory    IL1 and TNF and anti-inflammatory  IL10 that were measured by  ELISA.
After repeated administration of THC  for 10 days, in both young  and adult mice,  a significant  reduction in the production of IL2 and IFNγ was observable  . On the contrary, the levels of  IL4 appeared to have increased significantly .These data are consistent with the ability of THC to shift the Th1 / Th2  balance towards Th2.
 Then, to identify the long-term THC effects, we  immunized adult mice that had been  treated with THC for 10 days as adolescents (adolescent THC).In these animals we observed that  the production of cytokines IL2 and IFNγ was still very low compared to animals treated with vehicle; in these animals also the level of IL4 was  lower  compared with vehicle  mice.
A significant lower IgM titer was also present in these animals.
Regarding the macrophage function, repeated administration  of THC in both  young  and adult mice, induced a significant decrease of  IL1and increase of IL10. Particularly interesting were the results obtained in adolescent THC;in these animals we observed an inverted  effect since  IL1 increased and IL10 decreased.These resultsindicatethat theimmune systemisprofoundlyalteredby treatmentswithTHC, with thepresenceof aderegulatedresponse. We can conclude that the administration of THC has significant effects on the immune response that last long after administrationof THC.