Evaluation of systemic inflammatory response and lung injury induced by Crotalus durissus cascavella venom

Abstract

This study investigated the systemic inflammatory response and mechanism of pulmonary lesions induced by Crotalus durissus cascavella venom in murine in the state of Bahia. In order to investigate T helper Th1, Th2 and Th17 lymphocyte profiles, we measured interleukin (IL) -2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF) and interferon gamma (IFN-γ) levels in the peritoneal fluid and macerated lungs of mice and histopathological alterations at the specific time windows of 1h, 3h, 6h, 12h, 24h and 48h after inoculation with Crotalus durissus cascavella venom. The data demonstrated an increase of acute-phase cytokines (IL-6 and TNF) in the first hours after inoculation, with a subsequent increase in IL-10 and IL-4, suggesting immune response modulation for the Th2 profile. The histopathological analysis showed significant morphological alterations, compatible with acute pulmonary lesions, with polymorphonuclear leukocyte (PMN) infiltration, intra-alveolar edema, congestion, hemorrhage and atelectasis. These findings advance our understanding of the dynamics of envenomation and contribute to improve clinical management and antiophidic therapy for individuals exposed to venom.

Pulmonary involvement from animal toxins: the cellular mechanisms

“…Following toxin administration or bite, numerous in vivo studies and clinical cases have reported an elevation in proinflammatory cytokines [100] and clinical symptoms of SIRS which include severe outcomes such as cardiac and respiratory failure [101,102]. Similar observations have been noted in in vivo studies and human case reviews involving venom from snakes of the genera Crotalus [98,103],…”

“…If the inflammatory response outweighs the anti-inflammatory one and persists over time, multi-organ dysfunction may develop [ 96 ], including the aforementioned lung injury. Following envenomation, the histology of an alveolar epithelial cell revealed cellular senescence, polymorphonuclear cell infiltration, and fibrin deposition in the interstitial and alveolar spaces [ 19 , 97 , 98 ]. However, it is unclear whether the observed alveolar damage directly results from the venom components, an indirect effect mediated by inflammation, or both mechanisms [ 99 ] as most evidence comes from clinical observations and the detection of surrogate biomarkers for inflammation.…”

Snakebite Envenoming a Challenging Diagnosis for the Forensic Pathologist: A Systematic Review

“…The systemic inflammatory response and the mechanisms of pulmonary injuries by Crotalus durissus cascavella venom have been also investigated in mice by Azavedo et al (2020) [80]. They reported a significant increase of peribronchial inflammatory infiltrates, emphysema, and focal atelectasis indicative of severe pulmonary inflammation 3 h after venom injection followed by a decrease in the activity of inflammatory response, despite an increase in vascular congestion, alveolar septal thickening, and emphysematous areas at 6 h. Between 12 and 48 h, there were perceptible inflammatory infiltrates in the pulmonary parenchyma, hemorrhagic focuses, vascular congestion, and bronchial muscle distention [80].…”

Biological Effects of Animal Venoms on the Human Immune System

“…The effects of toxins isolated from the venom of bees and snakes have on the progression and development of symptoms in inflammatory and autoimmune disorders such as rheumatoid arthritis (RA) [ 79 ], acute intestinal inflammation [ 80 ], systemic lupus erythematosus (SLE) [ 81 ] and systemic inflammatory syndrome [ 82 ] have been evaluated. Thus, many modulatory effects have been studied, including the modulatory effects of cytokines.…”