Perturbations in Eosinophil Homeostasis following Treatment of Lymphatic Filariasis

Abstract

Treatment of patients with patent Wuchereria bancrofti infection results in an acute clinical reaction and peripheral eosinophilia. To investigate the dynamics of the eosinophil response, changes in eosinophil activation and degranulation and plasma levels of eosinophil-active chemokines and cytokines were studied in 15 microfilaremic individuals in south India by sequential blood sampling before and after administration of 300 mg of diethylcarbamazine (DEC). Clinical symptoms occurred within 24 h. Plasma interleukin-5 (IL-5) and RANTES levels peaked 1 to 2 days posttreatment, preceding a peak peripheral eosinophil count at day 4. Major basic protein secretion from eosinophils paralleled IL-5 secretion, while levels of eosinophil-derived neurotoxin peaked at day 13 after treatment. Expression of the activation markers HLA-DR and CD25 on eosinophils rose markedly immediately after treatment, while expression of VLA-4 and ␣4␤7 showed an early peak within 24 h and a second peak at day 13. Thus, the posttreatment reactions seen in filarial infections can be divided into an early phase with killing of microfilariae, clinical symptomatology, increases in plasma IL-5 and RANTES levels, and eosinophil activation and degranulation and a later phase with expression of surface integrins on eosinophils, recruitment of eosinophils from the bone marrow to tissues, and clearance of parasite antigen.

Eosinophil Activity inSchistosoma mansoniInfections In Vivo and In Vitro in Relation to Plasma Cytokine Profile Pre- and Posttreatment with Praziquantel

“…A transient infection intensity-dependent decline in peripheral blood eosinophil numbers shortly after treatment suggests that this immediate eosinophil response is dependent on the dose of worm antigen released by chemotherapy. Similar treatmentinduced eosinophil responses have previously been reported for filarial worm infections (1,16,18,26,41), but this is the first report of a reduction in circulating eosinophils in response to treatment of schistosomiasis. In contrast, the development of posttreatment eosinophilia has been reported for S. mansoni (36,37,48), Wuchereria bancrofti, and Onchocerca volvolus infections (16,18,26,27,42,48).…”

Chemotherapy for Schistosomiasis in Ugandan Fishermen: Treatment Can Cause a Rapid Increase in Interleukin-5 Levels in Plasma but Decreased Levels of Eosinophilia and Worm-Specific Immunoglobulin E

“…Nutman and colleagues (18,31) reported a similar peak in plasma IL-5 levels in the first few days after patients were treated for lymphatic filariasis with diethylcarbamazine. They also observed a decrease in circulating eosinophils immediately after treatment followed by an increase at least 4 days afterwards.…”

Localized Eosinophil Degranulation Mediates Disease in Tropical Pulmonary Eosinophilia

“…These data suggest that the release and production of the granular proteins are regulated differently. While it is unclear why EDN would have a special function in TPE, there are studies suggesting that eosinophilic granular proteins are under differential regulatory control, most notably following treatment for filarial infection (10). EDN has also been shown to have its own promoter, which is regulated by the transcriptional factor C/EBP, indicating that there may be differential transcriptional regulation of the eosinophil granule proteins (ECPs) (5).…”

“…IL-4, IL-5, and RANTES were measured using antibody pairs and techniques described previously (32). EDN and ECP measurements were performed as described previously (10), and the assay for BAL RNase was performed exactly as described previously (12,31).…”