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Thalassophryne maculosa fish envenomation is characterized by severe pain, dizziness, fever, edema and necrosis. Here, the dynamic of cellular influx, activation status of phagocytic cells, and inflammatory modulator production in the acute inflammatory response to T. maculosa venom was studied using an experimental model. Leukocyte counting was performed (2 h to 21 days) after venom injection in BALB/c mice footpads. Our results showed an uncommon leukocyte migration kinetic after venom injection, with early mononuclear cell recruitment followed by elevated and delayed neutrophil influx. The pattern of chemokine expression is consistent with the delay in neutrophil recruitment to the footpad: T. maculosa venom stimulated an early production of IL-1β, IL-6, and MCP-1, but was unable to induce an effective early TNF-α and KC release. Complementary to these observations, we detected a marked increase in soluble KC and TNF-α in footpad at 7 days post-venom injection when a prominent influx of neutrophils was also detected. In addition, we demonstrated that bone marrow-derived macrophages and dendritic cells were strongly stimulated by the venom, showing up-regulated ability to capture FITC-dextran. Thus, the reduced levels of KC and TNF-α in footpad of mice concomitant with a defective accumulation of neutrophils at earlier times provide an important clue to uncovering the mechanism by which T. maculosa venom regulates neutrophil movement.

Patients bitten by Loxosceles spiders generally manifest marked local inflammatory reaction and dermonecrosis. This report evaluated edema formation, leukocyte infiltration and release of inflammatory mediators at the injection site of Loxosceles gaucho venom. BALB/c mice were i.d. injected with venom and thereafter paws were disrupted and homogenized to obtain differential counts of migrated cells, as well to assay the levels of cytokines, chemokines and lipid mediators. Increased footpad thickness was detected as soon as 30 min after venom injection, and 24h later was similar to that of the control group. Loxosceles venom mildly augmented the recruitment of leukocytes to the footpad in comparison with PBS-injected mice. Moreover, it stimulated the release of IL-6, MCP-1 and KC at 2 and 24h after venom injection. In addition, higher levels of PGE(2) were detected 30 min after venom injection in comparison with control group. However, the venom failed to increase levels of IL-1 beta, TNF-alpha, TXB(2) and LTB(4). Our results demonstrate that L. gaucho venom evokes an early complex inflammatory reaction, stimulating the secretion of pro-inflammatory cytokines and lipid mediators (PGE(2)), and recruiting leukocytes to the footpad which contribute to the local reaction induced by L. gaucho venom.

Thalassophryne nattereri fish envenomation is commonly reported among fishermen and bathers in the Brazilian north and north-east coast, estimated at hundreds of accidents per year (Haddad et al. 2003). On Ceara State seaside, 16 cases of envenomation by T. nattereri were notified, from 1992 to 2002 (Faco et al. 2005). According to Fonseca and Lopes-Ferreira (2000), the palm of the hands or soles of the feet are the areas most commonly affected in the victims when pierced by spines connected to the fish's venom glands. Envenoming symptoms are readily evident, including local oedema, erythema and severe pain followed by intense necrosis and a markedly inefficient healing response. This problem of the inefficient healing is very important for the evolution and treatment of the accident, which is devoid of specific drug treatment (Lopes-Ferreira et al., 2000; Haddad et al. 2003). According to this, the symptoms advance, taking weeks or even months for complete recovery (Fonseca & Lopes-Ferreira 2000). Investigations carried out in our laboratory have shown that the dramatic symptoms of T. nattereri envenomation are related to kallikrein–kinin cascade, identified as the major mechanism involved in the nociception as well as the oedematous response to venom, as only the administration of novel tissue kallikrein inhibitor (phenylacetyl-Phe-Ser-Arg-N-(2,4-dinitrophenyl)-ethylenediamine – TKI), and not PKSI-527 and SBTI, specific and non-specific plasma kallikrein inhibitors, respectively, reduced these clinical manifestations (Lopes-Ferreira et al. 2004). Thalassophryne nattereri induces direct damage to skeletal muscle plasma membrane together with thrombosis and other alterations in the microvasculature of mice, without inducing haemorrhage (Lopes-Ferreira et al. 1998 2001). Analyses of the cremaster muscle showed that the venom elicits a peculiar alteration of the microcirculation with intense vascular congestion, thrombosis in venules and focal transient constrictions in arterioles (Lopes-Ferreira et al. 2002). In contrast to other models of myonecrosis, in which the microvasculature is not affected, phagocytosis of necrotic material is well advanced by 24 h and no remnants of necrotic muscle cells are observed after 1 week (Harris et al., 1975; Gutierrez et al., 1991; Morini et al., 1998. Curiously, low numbers of phagocytic cells during the first 24 h after)T. nattereri injection, and the presence of necrotic material which had not been cleared out 7 days after envenomation was described (Lopes-Ferreira et al. 2001; Lima et al. 2003). Nevertheless, the reason that the venom toxins favour delayed local inflammatory response is ill defined. This study was carried out to describe leucocyte movement into mice tissue after the injection of T. nattereri venom in order to investigate the role of inflammatory mediators, metalloproteinases and cell adhesion to extracellular matrix (ECM) components present in this envenomation.

Phyllomedusa hypochondrialis skin secretion can cause both systemic and local effects. In this study, we describe the pattern of local acute inflammatory response after P. hypochondrialis skin secretion injection. The inflammatory reaction in the mice footpad was analysed, including the leukocyte recruitment into local tissue from the peripheral blood, in a mouse model of tissue injury. We also investigated the release of the cytokines IL-1, IL-6 and TNF- α , chemokines KC and MCP-1 and the eicosanoids LTB 4 and PGE 2 in mice. The present findings support the ability of P. hypochondrialis skin secretion to induce local inflammation. In addition, these skin secretion components play a role in the initial rolling and slowing of recruited leukocytes and the transition from rolling to adhesion. Levels of the proinflammatory cytokine IL-6, chemokines KC and MCP-1 as well as the eicosanoid PGE 2 were significantly increased after injection of a skin secretion of P. hypochondrialis (0.6 μg/30 μl intraplantar), whereas no changes in other parameters were observed. Finally, the mechanisms involved in the local inflammatory process induced by P. hypochondrialis skin secretion is one of the questions of relevance related to the complex pathophysiology induced by this particular secretion and other toxins.