Neurocysticercosis: the effectiveness of the cysticidal treatment could be influenced by the host immunity

Abstract

Neurocysticercosis, a clinically and radiologically pleomorphic parasitic disease, is still endemic to most non-developed countries of Latin America, Africa, and Asia. Anti-helminthic drugs (AHD) are generally effective and rapidly destroy parenchymal cysticerci. In contrast, several cycles of AHD are frequently necessary to damage extraparenchymally located parasites. The present study was designed to evaluate whether differences in the immunological profile of the patients is involved in the diversity of the response to AHD. To this end, a global gene expression microarray and a cytokine analysis were made. Responder patients were those showing a radiological reduction greater than 50 % in the parasite burden following AHD treatment. Microarray pre- and post-treatment comparisons showed that a total of eighteen immune-related genes were up-regulated in the five responder patients with respect the expression profile seen in the four non-responder subjects. The function of up-regulated genes exerted pro-inflammatory (RORγC, Sema4A, SLAMF3, SLAMF6), anti-inflammatory (TGFβ, TNFRSF25, TNFRS18, SLAMF1, ILF2), or immunomodulatory effects (CXCL2, RUNX3, SLAMF9, TGFBR3). To further explore the causes of the heterogeneity in the response to treatment, a wide ELISA cytokine analysis was performed in serum, PBMC supernatants, and CSF samples from 39 responder and 26 non-responder patients. Responder patients showed higher CSF IL-17A levels (P = 0.04) and higher supernatant IL-6 levels (P = 0.03) 60 days after treatment. These results suggest a possible influence of pro-inflammatory cytokines on the response to AHD as observed by radiological methods, and thus the possible participation of the host immunity in the effectiveness of AHD treatment.

Treatment-Resistant Human Extraparenchymal Neurocysticercosis: An Immune-Inflammatory Approach to Cysticidal Treatment Outcome

“…The previously reported Treg differentiation in vitro driven by cysticerci supports this possibility [17]. Additionally, the inflammatory immune response influences both clinical manifestations in NC patients [9,16,18,26] and the response to cysticidal treatment, possibly related with higher IL-17 and IL-6 levels [9]. In concordance with this, we found lower IL-6 levels in resistant patients with respect to controls.…”

“…Most of these NC patients show higher central Treg percentages, which positively correlated with Treg peripheral levels [14]. These cell subtypes tightly control inflammation, and it has been proposed that an inflammatory status is required for the cysticidal treatment to be effective [9]. Considering the influence of catecholamines on the inflammatory response, we focused on cysticidal treatment resistant-NC patients.…”

“…Nevertheless, these drugs are not effective in all NC patients, particularly in those cases where cysts are established in the ventricles or in the subarachnoid space of the base [5][6][7][8]. Some evidence that the immunity-mediated inflammation observed during NC infection is involved in treatment responsiveness has been recently published [9]. The need for administering high corticosteroid doses to avoid possible life-threatening complications due to exacerbated neuroinflammation, such as acute hydrocephalus and secondary vasculitis, stresses the relevance of the latter finding.…”

Extraparenchymal neurocysticercosis: Demographic, clinicoradiological, and inflammatory features

“…At a radiological level, although most parasites were racemose, about 20% of patients presented a single parasite. The consequences of this variability are not completely understood, but it could be involved in the heterogeneity of the response to treatment and in the varying success of such treatment, as previous studies indicate [44, 45]. Further analysis is required to better understand this aspect.…”

Comparison of monocyte gene expression among patients with neurocysticercosis-associated epilepsy, Idiopathic Epilepsy and idiopathic headaches in India

“…For example, Cardenas et al detected differential expression of immune-response genes in Taenia -antigen stimulated peripheral blood mononuclear cells from NCC patients who did or did not demonstrate radiological response to anti-helminthic drug treatment [10]. It has also been reported that the network of monocytes and astrocytes play a role in the inflammatory response to intraparenchymal cysts of NCC [11, 12]. Furthermore, other studies show that blood monocytes produce bioactive mediators including CXCL8 (IL-8), CCL2 (MCP-1) and TNF-α, in response to stimulation with T .…”