Leishmania Amastigotes Induced Remission of Cutaneous Leishmaniasis, Psoriasis, Psoriatic Arthritis and Related Diseases

Abstract

Amastigotes from L(L) amazonensis (La); L(L) venezuelensis (Lv); L(V) brasiliensis (Lb) and L(L)chagasi(Lch) were cultured axenically in a liquid culture medium (O’Daly’s medium). Patients from a cutaneous leishmaniasis (CL) endemic and hyperendemic regions in Venezuela, receiving different treatments were followed up for 6 years. Remission of lesions (weeks) were: Spontaneous remission (SR): 7; Glucantime® (Glu) chemotherapy: 9; Immunotherapy with La, Lv, Lb, Lch amastigotes Tosyl-Lysil-Chloromethyl-Ketone (TLCK) treated and Nonidet P-40 (NP-40) extracted (AS100-1VT): 7. While vaccinating subjects for CL protection, we observed 100% clinical remission of a psoriatic lesion in one subject. In an open trial, 2,770 subjects showed baseline psoriasis area and severity index (PASI) compared with post-treatment values as follows: PASI 100, 23%; PASI 75, 45%; PASI 50, 13%; PASI 10, 9% and <PASI 10, 3% of patients, without serious adverse events. Similar results were obtained with AS100-2 La, Lv, Lb and Lch monovalent vaccines. After treatment with AS100-1VT, subjects with psoriatic arthritis (PsA) decreased in arthritis score, tender joints counts and nail changes; the highest decreased in the PASI 100 group. The vaccines induced cellular immunity with absence of humoral antibody responses. Lymphocyte subsets (LS) in peripheral blood mononuclear cells (PBMC) decrease as PASI increased migrating from the blood to the skin/joints. After vaccine treatment the LS migration is stopped explaining remission of lesions. Purified Leishmania antigenic fractions (AS200) induced linear delayed type hypersensitivity reactions (DTH) in guinea pigs. A DBA-1 mouse collagen induced arthritis (CIA) model with AS200 treatment had the least amount of forepaw inflammation and the lowest arthritis scores, lower than dexamethasone. The vaccines AS100-1VT, AS100-2 and AS200 were not immunosuppressors, but immunomodulators decreasing inflammatory cytokines. The aim of this review is to explain the serendipity discovery of leishmania parasites inducing remission of psoriasis and related diseases, unprecedented discovery in the scientific literature.