Caterpillar is the larval stage of butterflies and moths. These animals are widespread in various ecosystems. Upon contact with the skin, some caterpillars release venoms and cause reactions, such as itching, pain, even a systemic response. Actual symptoms depend on the species, the amount of toxin that enters the body and the victim’s physical condition (health, age, weight).

Caterpillars’ venoms have not been studied as extensively as those of snakes, scorpions, spiders and bees as only few species of butterflies and moths (order Lepidoptera) are venomous for humans. Among the caterpillar venoms studied are those of the genera Thaumetopoea, Euproctis and Lonomia. The majority of encounters occur with exposure to the caterpillar’s urticating hairs or bristles, but hemolymph can also have toxic properties.

Thaumetopoea

The larvae of this family are best known as processionary caterpillars. They mostly live in webs which they leave at night to feed on leaves. When moving, they crawl one behind the other, forming rows or columns. They occur in the Palearctic, Oriental, European and Ethiopian regions, they feed on pines, oaks and, less commonly, on cedars and walnut. The caterpillars have urticating hairs. Venom is drawn by capillary action into the tip of the hair from glands in the epidermis. In adults there are sockets in the abdomen which also release the hairs. Pruritic dermatitis and urticaria result from contact with the larvae, airborne setae from the adults, or contact with eggs in which the hairs from the female have been incorporated as a protective covering. Skin tests have confirmed that the urticant substance is histamino-liberating.

Thaumetopoea processionea is widely distributed in Europe, where it commonly causes urticaria. Other processionary caterpillars which cause discomforting rashes include Anaphe infracta in Europe and T. wilkinsoni in Africa and Madagascar.

Euproctis

Euproctis chrysorrhoea is a moth of the family Erebidae. It is native to Europe, neighboring countries in Asia and the north coast of Africa. Hairs from the caterpillars are toxic for humans, causing an itchy rash of up to sometimes weeks-long duration due to mechanical and chemical irritation. Direct contact with larvae is not necessary, as the hairs are shed and can become windblown. Toxins in the hairs remain potent for up to three years. Outdoor activities such as mowing a lawn or raking leaves in autumn can cause exposure. People suffer from dermatitis caused by the contact with this moth.

Lonomia

Genus Lonomia (family Saturniidae) is one of the largest groups of butterflies. They are widespread around the world and are most common in tropical and subtropical regions. Caterpillar incidents are recorded only in South America. The occurrence of hemorrhagic syndrome in humans is known only for the species Lonomia obliqua (southern Brazil) and L. achelous (northern Brazil and Venezuela).

Among all the lepidopterans of medical interest Lonomia is the only genus that causes dramatic damages in human blood coagulation. Lonomia obliqua is classified as the most venomous caterpillar in the world.

Venom and its effect

Venom is stored in sacks at the base of each bristle. The distal end of the bristle is thin, chitinous and breaks easily, releasing venom through canal into the puncture wound. These structures are present in all larval stages.

Venoms of both species of caterpillars have different composition and also work differently, but the effects are similar. Venoms with coagulation and anticoagulant effects predominate. L. obliqua venom has procoagulant activity, while L. achelous has both; procoagulant and anticoagulant effect.

The main symptoms of progressive intoxications are disorders of blood clotting, spontaneous bleeding from the mucous membranes and from pre-existing wounds. Intoxication also leads to brain damage, which can lead to death. Fatality is about 2 % due to cerebral hemorrhage.

• L. achelous venom causes hemorrhagic syndrome, the main mechanism of action is fibrinolysis. The venom also has coagulation activity. Serine protease toxins are present in hemolymph and, consequently, in the venom, they degrade extracellular matrix proteins such as laminin, vitronectin and fibronectin. These toxins contribute to hemorrhagic events, because they contribute to the spread of the venom throughout the victim’s body and increase bleeding due to capillary damage.

• L. obliqua venom causes blood coagulation which results in fibrinolysis and this causes symptoms of hemorrhage. Venom consists mostly of procoagulation components (Lopap, Losac), which trigger a blood clotting cascade, thus  removing prothrombin and the resulting fibrin is deposited on the walls of blood vessels. Severe intravascular coagulation may result. The main effects of the venom are: reduced or prevented blood coagulation in the event of injury and the occurrence of spontaneous bleeding. Hemolysis and fibrinolysis may also occur.

An antidote has been produced, it works by inhibiting blood coagulation. Although it causes significant side effects, it is used because no other treatment is known. Patients treated such way recover faster than if they had not been treated.

Usage of L. obliqua venom

L. obliqua venom has been studied extensively to determine its medical value. Studies on these toxins show potential of specific component usage beyond the pathophysiology and therapeutic perspectives of envenoming, because procoagulant proteins, Lopap and Losac, can be useful as tools for developing clotting assays and diagnostic kits. Exogenous procoagulant proteins could also be considered for therapeutic use to manage bleeding complications caused by anticoagulation therapy.

The component Lopap (L. obliqua prothrombin activator protease) usage:

• anticoagulant and anti-apoptotic qualities;
• as therapeutic agents for use in defibrinogenating and antithrombotic therapy;
• the effects of Lopap on extracellular matrix remodeling can be valuable to develop wound healing formulations and for regeneration issues;
• for promoting wound healing (Lopap- and Losac-derived peptides).

Modulation of cell responses triggered by Lonomia toxins can have valuable therapeutic and biotechnological applications. Promoting cell survival can be useful to improve cell culture technologies, vaccine productions and for treatment of degenerative diseases.

Conclusion

Undestanding the mechanisms of action and structure-function relationship of these multifunctional molecules may highlight these molecules as potential components to development of new therapeutic drugs, reagents in diagnostic kits for coagulation dysfunctions and biotechnological applications.

Two hyaluronidases in L. obliqua venom have been described. The enzyme was named Lonogliaza. Hyaluronidases are likely to contribute to local effects caused by the venom. Hyaluronidases in the venom are of great interest as they are thought to have an effect on cancer cell growth and tumor invasion and serve as a tool in cell biology research.

Sources:

• A. M. Chudzinski-Tavassi, M. P. Alvarez-Flores, L. Christian Carrijo-Carvalho, M. Esther Ricci-Silva. Toxins from Lonomia obliqua — Recombinant Production and Molecular Approach. 2012 https://www.intechopen.com/chapters/45118
• C. S. Malaque, I. Andrade, G. Madalosso, S. Tomy, F. I. Tavares, A. C. Seguro. A case of hemolysis resulting from contact with a lonomia caterpillar in southern brazil. 2006
• M. P. Alvarez-Flores, R. N. Gomes, D. Trevisan-Silva, D. S. Oliveira, I. F. C. Batista, M. V. Buri, A. M. Alvarez, C. DeOcesano-Pereira, M. M. de Souza, A. M. Chudzniski-Tavassi. Lonomia obliqua Envenoming and Innovative Research. 2021
• https://www.sciencedirect.com/topics/immunology-and-microbiology/thaumetopoea
• https://en.wikipedia.org/wiki/Brown-tail_moth