Role of galanin receptor 2/3 in inflammation associated with peritonitis

Peritonitis poses a serious medical challenge due to abdominal wall inflammation, often triggered by infectious agents. Understanding its immunological mechanisms is crucial for innovative therapies. The regulatory peptide galanin and its receptors (GAL1-3-R) are expressed on various immune cells and play pivotal roles in inflammation. The impact of GAL2/3-R knockout (KO) was assessed in a preclinical peritonitis model, using aged 4% thioglycollate medium (TGM) injected intraperitoneally in GAL2/3-R KO and corresponding WT mice. Comparison to vehicle controls was included to discern treatment-specific effects. After 6 hours, peritoneal fluid, spleen and blood cells were collected. Chemokine levels in the peritoneum were assessed via multiplex immunoassays. Notably, in GAL2/3-R KO mice the induction of chemokines, especially RANTES, IP-10, and MIG, upon TGM treatment was less prominent compared to WT mice. Simultaneously, increased levels of peritoneal macrophages were detected by flow cytometry. Immunophenotyping of blood and spleen revealed reduced neutrophil levels in both compartments upon induction of peritonitis in GAL2/3-R KO mice, accompanied by elevated dendritic cells in the blood. The observed alterations in chemokine levels and immune cell populations specifically in GAL2/3-R KO mice suggest a regulatory role for GAL2/3-R in modulating the immune response in peritonitis. Consequently, antagonism of GAL2/3-R could potentially dampen the sometimes overshooting immune response observed in peritonitis, thus representing a promising avenue for therapeutic interventions.