Mouse anti Human IFNG monoclonal antibody, clone L4.64

Trypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries. There is some evidence that there is diversity in the disease progression of T.b. rhodesiense in different countries. HAT in Malawi is associated with a chronic haemo-lymphatic stage infection compared to other countries, such as Uganda, where the disease is acute with more marked neurological impairment. This has raised the question of the role of host genetic factors in infection outcomes. A candidate gene association study was conducted in the northern region of Malawi. This was a case-control study involving 202 subjects, 70 cases and 132 controls. All individuals were from one area; born in the area and had been exposed to the risk of infection since birth. Ninety-six markers were genotyped from 17 genes: IL10, IL8, IL4, HLA-G, TNFA, IL6, IFNG, MIF, APOL, HLA-A, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH. There was a strong significant association with APOL1 G2 allele (p = 0.0000105, OR = 0.14, CI95 = [0.05-0.41], BONF = 0.00068) indicating that carriers of the G2 allele were protected against T.b. rhodesiense HAT. SNP rs2069845 in IL6 had raw p < 0.05, but did not remain significant after Bonferroni correction. There were no associations found with the other 15 candidate genes. Our finding confirms results from other studies that the G2 variant of APOL1 is associated with protection against T.b. rhodesiense HAT.

Murine/LPS models of Gram negative sepsis indicate that vasoactive intestinal peptide (VIP) has therapeutic potential. We investigated the unknown effect of VIP on JAK/STAT proteins and genes in human monocytes infected with Salmonella Typhimurium 14028. S. Typhimurium 14028 increased expression of both IL-6 receptor (IL-6R) and interferon gamma receptor 1 (IFN gamma R1) on monocytes but co-culture of infected monocytes with VIP (10(-7) M) only decreased expression of IFN gamma R1 (P < 0.05). In contrast, S. Typhimurium 14028 infection or co-culture with VIP had no effect on IL-10 receptor expression on the monocyte surface. However, S. Typhimurium 14028 down regulated IFNGR1 gene expression and this was not altered by co-culture with VIP, suggesting that changes in IFN gamma R1 protein may be due to an effect on cytoplasmic transport. 15 JAK/STAT genes, out of 84 studied, were up-regulated by S. Typhimurium 14028 infection and five were down-regulated. Co-culture with VIP significantly decreased expression of two genes (IFNG and IL-20) and increased expression of three genes (SOCS1, SOCS3 and STAT4) (P < 0.05). S. Typhimurium 14028 also increased expression of PTPN1, which dephosphorylates JAK2 and TYK2. This was unaltered by co-culture with VIP but S. Typhimurium 14028-induced expression of ISG15, associated with susceptibility to Gram negative infection, was further increased by VIP. We conclude that the effect of VIP on JAK/STAT genes may preclude its therapeutic use in human Gram negative sepsis.