Immunomodulatory activity of diethylcarbamazine on humoral, cellular cytokine response and respiratory burst in BALB/c mice

Abstract

Diethylcarbamazine (DEC) is an anthelmintic piperazine derivative drug with putative immunomodulating properties, including increased platelet and granulocyte adhesion to parasites and enhanced production of cytokines. To further analyse these properties in a well-established animal model, we evaluated the effect of DEC on antibody, cellular cytokine response and respiratory burst in BALB/c mice. Animals were challenged with a thymus-dependent (tetanus toxoid, (TT)) and with a thymus-independent (lipopolysaccharide, (LPS)) antigen and treated with DEC for seven days with two different doses (50 mg/day and 500 mg/day). Serum was assessed for antibody production at 0, 4, 7, 14, 21 and 28 days after stimulation and at 0, 24 and 48 h for IL-2, IFN-γ, IL-10 and IL-12 release. Respiratory burst of neutrophils and monocytes from peripheral blood was measured by flow cytometry. We found low-dose treatment with DEC enhanced cytokine production vs. TT and antibody production vs. LPS, whereas a higher dose enhanced significantly the respiratory burst of both polymorphonuclear leukocytes and monocytes, with a significant higher effect on the former. Our results suggest a stimulating, dose-dependent immunomodulatory effect of DEC with a higher effect on the phagocytic cells.

Immunomodulatory effect of diethylcarbamazine in mice infected with Nocardia brasiliensis

“…Thus, the acquired immunity may control bacterial growth and help to eliminate bacteria and resist to infection, thus inhibiting a further development of lesion. Although an increased production of antibodies under DEC treatment has been shown before [9,10], we did not find any correlation between IgG and IgM antibody production and the protection given by DEC administration. Resistance to intracellular microorganism infections involves most immune effectors and principally T cells.…”

“…The influence of DEC in an infectious model produced by N. brasiliensis seems to confirm in vivo the positive immunomodulatory effect observed earlier where oxidative burst was increased in both monocytes and granulocytes after DEC therapy [10]. In spite of it, in our actual study although an enhancement of monocyte oxidative index was not demonstrated in vitro, the striking modification of the lesion was evident, suggesting an in vivo action on cellular effectors of host after drug administration [10].…”

“…In spite of it, in our actual study although an enhancement of monocyte oxidative index was not demonstrated in vitro, the striking modification of the lesion was evident, suggesting an in vivo action on cellular effectors of host after drug administration [10].…”

“…An adjuvant effect of DEC associated with fluconazole has also been shown as diminished levels of fungi in brain and kidney of treated compared with non-treated mice [9]. We recently evaluated the cellular, humoral responses and phagocytosis in an immunocompetent BALB/c mouse model under DEC treatment, where an increasing response of respiratory burst in polymorphonuclear and monocytes, and increased IL-2 production were identified [10]. Further on DEC effect on cells, Peixoto and Silva have recently reviewed the subject focusing on the interference of the drug on cyclooxigenase and lipooxigenase pathways and on the inhibition of NF-kB signaling cascade [11].…”

Immunoadjuvant effect of diethylcarbamazine in experimental filariasis

“…DEC has already been shown to possess immunomodulatory effects in respiratory burst in BALB/c mice [19], bacterial and fungal infections [11]. In viral infections such as feline leukemia virus (FeLV) in cats [10] and Human Immunodeficiency Virus (HIV) [9], DEC has exhibited adjuvant effect by enhancing the humoral and cellular response towards elimination of the virus.…”