“Scientists have made a breakthrough which could reduce the risk of children suffering serious allergic reactions to peanuts and other food,” BBC News reported. It said that researchers have identified a new chemical that plays a key part in the development of anaphylaxis, a severe, potentially life-threatening allergic reaction.
These experiments in mice demonstrated the key role of IL-33, a newly discovered chemical (called a cytokine) involved in immune responses, in causing an anaphylactic reaction. These important findings suggest that this cytokine could be a potential target for the future treatment of anaphylaxis. It is important to note, however, that these are animal experiments, which means a human application may be some time away.
The study was carried out by Dr Peter Pushparaj and colleagues from the University of Glasgow, the National University of Singapore and the Medical Research Council Laboratory of Molecular Biology in Cambridge. The research was funded by grants from the Wellcome Trust and the Medical Research Council. It was published in the peer-reviewed medical journal: PNAS (Proceedings of the National Academy of Sciences).
This study investigated the role of a cytokine, called cytokine interleukin-33 (IL-33), in allergic reactions. Cytokines are chemicals that play a role in the functioning of the immune system. The researchers examined levels of IL-33 in serum and tissue from patients having anaphylactic and allergic responses. Their findings from these observations in humans led them to test their theories in experiments on mice.
Very simply, parts of the immune system are activated by the presence of an antigen (a substance that provokes an immune response), which stimulates the production of an antibody to that antigen. An important antibody that is elevated in the blood of people with allergies is the IgE antibody. This antibody is specific to whatever type of antigen induced its release and it acts to remember the exposure so that future exposures result in a strong allergic response to that challenge.
In their animal experiments, the researchers sensitised some mice with IgE antibody, with the aim of inducing a response to a particular antigen called dinitrophenyl-human serum albumin (DNP-HSA). A day later, the mice were exposed intravenously to several different antigens, including DNP-HSA, IL-33 (the new cytokine) or IL-33 plus DNP-HSA. The level of vascular permeability was then compared between the mice in the different exposure groups. Vascular permeability is a measure of the level of small molecules (e.g. nutrients, water and blood cells) that can pass through small blood vessels. During an allergic response, vessels become more permeable. Further experiments were undertaken to determine which immune cells were involved in the immune response.
The researchers observed that people who developed anaphylactic shock in the operating theatre had higher levels of several chemicals associated with allergy, including IgE and IL-33, compared to healthy people and to those with allergies, but who had not developed anaphylaxis. Higher levels of IL-33 were also evident in the skin lesions of people with atopic dermatitis (a type of eczema) compared with non-inflamed skin samples.
Sensitised mice that were exposed to DNP-HSA (an allergen) showed expectedly raised levels of vascular permeability, while those who were not sensitised showed no response to any of the three allergens. However, sensitised mice exposed to IL-33 showed a similar increase in vascular permeability and this effect was more extreme when the sensitised mice were exposed to both IL-33 and DNP-HSA. IL-33 triggered anaphylactic shock in these mice, leading to a rapid drop in body temperature, increased histamine levels and inflammation in the lungs.
Importantly, further detailed experiments revealed that IL-33 may be responsible for ‘tipping the balance’ of the mast cells (which play a key role in inflammation) from ‘helpful’ to ‘harmful’ allergic responses and may therefore represent a potential target for treatment of anaphylactic shock.
Observations in humans suggest that IL-33 is raised in allergic patients during an allergic-inflammatory response. Furthermore, IL-33 can trigger anaphylactic responses in mice that are IgE sensitised, demonstrating the key role that this cytokine plays in allergies. IL-33 may be a potential target for treating allergic shock.
These animal experiments further the understanding of the workings of complex immune systems in the body. Their direct relevance to allergic reaction in humans is unclear as the studies are in mice. However, observations in humans with allergies or in humans who were experiencing anaphylactic shock support the theory that IL-33 plays a key role in severe allergic responses.
The researchers say that it is not possible from their observational human data to know whether IL-33 was produced in response to the allergic reaction or whether it caused it. They also note that they only reviewed data from allergic patients who developed anaphylactic shock during surgery, and while they say that IL-33 may indeed be elevated in other inflammatory conditions such as peanut or drug-induced anaphylactic shock, this is currently being investigated.
Overall, the findings from this study will be of particular interest to scientists who are trying to understand how the immune system functions. It may one day lead to novel ways to treat allergic conditions, but these are still some time in the future.