The Catecholamine Cytokine Balance: Interaction between the Brain and the Immune System

doi:10.1196/annals.1391.026

Cytokines are involved both in various immune reactions andin controlling certain events in the central nervous system(CNS). In our earlier studies, it was shown that monoamine neurotransmitters,released in stress situations, represent a tonic sympatheticcontrol on cytokine production and on the balance of proinflammatory/anti-inflammatorycytokines. Basic and clinical studies have provided evidencethat the biophase level of monoamines, determined by the balanceof their release and uptake, is involved in the pathophysiologyand treatment of depression, while inflammatory mediators mightalso have a role in its etiology. In this work, we studied therole of changes in norepinephrine (NE) level on the lipopolysaccharide(LPS) evoked tumor necrosis factor (TNF)- ${alpha}$ and interleukin (IL)-10response both in the plasma and in the hippocampus of mice.We demonstrated that the LPS induced TNF- ${alpha}$ response is in directcorrelation with the biophase level of NE, as it is significantlyhigher when the release of NE of vesicular origin was completelyinhibited in an animal model of depression (reserpine treatment)and it is significantly lower in the case of increasing biophaselevels of NE by genetic (NET–KO) or chemical (desipramine)disruption of NE reuptake. IL-10 was changed inversely to TNF- ${alpha}$ levels only in the desipramine-treated animals. Our resultsshowed that depression is related both to changes in peripheraland in hippocampal inflammatory cytokine production and to monoamineneurotransmitter levels. Since several anti-inflammatory drugsalso have antidepressant effects, we hypothesized that antidepressantsare also able to modulate the LPS-induced inflammatory response,which might contribute to their antidepressant effect.

Part VI. Psychosocial Stress

Interaction between the Brain and the Immune System