Levamisole enhances the innate immune response and prevents increased cortisol levels in stressed pacu ( Piaractus mesopotamicus )

Abstract

We analyzed the effects of levamisole on stress and the innate immune responses of pacu (Piaractus mesopotamicus). A total of 300 fish (180 ± 1.27 g) were fed a diet containing levamisole hydrochloride (LHC) for 15 days, then distributed into the following groups: T0 (control group); T1 (100), T2 (150), T3 (300) and T4 (500) mg kg LHC (15 fish per group and four replicates per treatment). After this, fish (n = 8 per treatment) were exposed to air for three minutes to simulate stress conditions and were then challenged with the bacterium Aeromonas hydrophila to stimulate the immune system. Fish were sampled at 1, 3 and 24 h after bacterial inoculation to measure plasma cortisol and glucose concentrations, the leukocyte respiratory burst (LRB), hemolytic activity of the complement system (HAC) and serum lysozyme activity (SLA). LHC attenuated the increase in plasma cortisol at 1 h (500 mg kg) and 3 h (300 mg kg) after air exposure and bacterial inoculation compared to control fish. The highest glucose concentrations were observed at 1 and 3 h after stress, which then returned to initial levels after 24 h, without any effect of LHC. The LHC 100 mg kg dose increased LRB 1 h after inoculation and activated the HAC 3 h later. At 24 h, all LHC concentrations increased the HAC. SLA was reduced after inoculation, throughout the experimental period, without an effect of levamisole. Our results indicate that the oral administration of levamisole for 15 days modulated circulating cortisol levels during the stress response and improved the innate immune response against A. hydrophila infection in pacu.

Levamisole modulates cortisol and innate immunity responses in tambaqui ( Colossoma macropomum ) parasitized with Neoechinorhynchus buttnerae

“…In stressed fish, cortisol concentrations increased, particularly in those fed with 500 mg LHC, suggesting a higher ability to respond to the stressor. Glucose concentration was not affected by levamisole in both experiments, as previously shown in pacu (Pahor‐Filho et al, 2017). The activation of the complement system was associated with the levamisole but not with cortisol, although cortisol has been shown to modulate the immune system in fish, including the complement system (Tort, 2011).…”

“…T0 (control), T1 (100 mg kg −1 ), T2 (300 mg kg −1 ) and T3 (500 mg kg −1 ). The absence of letters indicates no significant differences not affected by levamisole in both experiments, as previously shown in pacu (Pahor-Filho et al, 2017). The activation of the complement system was associated with the levamisole but not with cortisol, although cortisol has been shown to modulate the immune system in fish, including the complement system (Tort, 2011).…”

“…The pathogenicity of Acanthocephala depends on the degree of proboscis penetration, among other factors (Jerônimo et al, 2017), a stressful condition that makes fish more susceptible to stress during the management (Maciel et al, 2008). LHC reduced the circulating cortisol, indicating a stress-reducing effect as described in pacu (Pahor-Filho et al, 2017) and rats (Stogaus & King, 1995) fed with LHC. In less infected fish, cortisol concentrations did not change after feeding with LHC, suggesting that the intensity of infection was not a stressor, probably because when the parasitehost interaction is well established, there is no stress effect in fish (Schalch et al, 2005).…”

“…Therefore, the use of immunostimulants to enhance resistance against pathogens and feed additives to mitigate stress has increased (Herrera et al, 2019; Vallejos‐Vidal et al, 2016). Levamisole hydrochloride (LHC) is an anthelmintic used to control parasitosis in fish (Guz et al, 2015; Taraschewsk et al, 1988), which has shown to activate immunity in fish (Biller‐Takahashi et al, 2016; Cuesta et al, 2002; Pahor‐Filho et al, 2017) and promote a stress‐reducing effect (Pahor‐Filho et al, 2017). The tambaqui ( Colossoma macropomum ) is a native fish that is boosting Brazilian aquaculture (Saint‐Paul, 2017).…”

Stress management in aquaculture: a review of dietary interventions

“…In a recent study, 0.1% levamisole supplementation in commercial diet improved high-density stress tolerance in rainbow trout (Meshkini et al 2017). Dietary levamisole administration modulated the circulating levels of cortisol during acute air exposure stress in pacu and enhanced the innate immune response against bacterial challenge (Pahor-Filho et al 2017b). An earlier study in levamisole-fed antigen challenged rat also reported a reduction in plasma corticosterone levels and is corroborated to the immunostimulatory effect of levamisole (Stogaus & King 1995).…”