Several studies have indicated that influenza vaccination can protect the heart, and this has also led to a change in cardiology guidelines in Europe this year. Now researchers will investigate whether influenza vaccination can also protect the insulin-producing cells in the pancreas of children with new-onset type 1 diabetes.
In its latest guidelines, the European Society of Cardiology recommends that people hospitalised with a heart attack receive influenza vaccination before being sent home. People who have previously had a heart attack are also recommended to get influenza vaccination every year.
These recommendations are based on very interesting studies showing that influenza vaccination not only protects against influenza but is also associated with several nonspecific effects that appear to both protect against cardiovascular disease and type 1 diabetes and have possible positive effects on cancer and nervous system diseases such as Alzheimer’s.
Researchers will now investigate the potential of protecting against type 1 diabetes in a major study in Denmark in which children with new-onset type 1 diabetes will receive influenza vaccination to determine whether this helps to slow the development of the disease.
“Influenza vaccination has an immunomodulatory effect as part of creating a response against influenza, and this appears to protect against several other diseases,” explains Mads Fuglsang Kjølby, doctor and Associate Professor from Steno Diabetes Center Aarhus and the Department of Clinical Pharmacology at Aarhus University Hospital.
“We hope that this may slow down the destruction of the insulin-producing cells of children with new-onset type 1 diabetes so that they can retain some of their insulin production, which will greatly improve their lives and treatment,” adds Astrid Johannesson Hjelholt, doctor and Postdoctoral Fellow, also from Steno Diabetes Center Aarhus and the Department of Clinical Pharmacology at Aarhus University Hospital.
Mads Fuglsang Kjølby, Astrid Johannesson Hjelholt and colleagues recently published a review in Vaccines on the nonspecific effects of influenza vaccination.
Mads Fuglsang Kjølby is also one of the researchers behind the potentially pioneering trial involving children with type 1 diabetes.
Modulating the immune response
Influenza vaccination can affect other factors than the risk of getting influenza because the vaccine has an immunomodulatory effect.
Immunomodulation means upregulating or downregulating the part of the immune system called cytokines.
In the review article, the researchers indicate that a study in Science has shown that, for people with type 1 diabetes, developing drugs that bind to various cytokines and either activating them agonistically or inhibiting them antagonistically may be appropriate.
The cytokines that should be upregulated to reduce overall inflammation are interleukin 6 (IL-6), IL-8 and tumour necrosis factor (TNF)-alpha, and IL-2 and IL-10 should be downregulated.
Influenza vaccination does this by upregulating I-L6, IL-8 and TNF-alpha and downregulating IL-2 and IL-10.
“The fact that influenza vaccination costing DKK 25 can hit all the targets that seem to be relevant for developing type 1 diabetes is very promising,” says Astrid Johannesson Hjelholt.
Protective effects of vaccination after a heart attack
A European study with 2,571 patients hospitalised for treatment after a heart attack investigated the potential of the nonspecific effects of influenza vaccination.
The participants received either influenza vaccination or placebo within 72 hours of balloon angioplasty before being discharged.
The researchers followed the participants for 12 months, and the people who had received influenza vaccination had a 41% lower risk of death and a lower risk of experiencing a new heart attack or a further clot in a treated artery.
Of the vaccinated participants, 2.9% died during the 12 months versus 4.9% of those in the placebo group.
The results subsequently led to a recommendation that everyone hospitalised with a heart attack or who previously had a heart attack should receive influenza vaccination.
“The study showed that the effects occur quite early, which is difficult to explain in terms of a protective effect against influenza. If you link the results to those of other studies, influenza vaccination instead appears to create a favourable cytokine profile, which protects the heart and perhaps also protects against more than just influenza and cardiovascular disease,” explains Astrid Johannesson Hjelholt.
Major trial among children with type 1 diabetes
Based on the evidence from the studies included in the review and the positive results from the trial involving people with a previous heart attack, the researchers from Aarhus University along with international colleagues, including colleagues from that trial, have started a new trial in which they will give children with new-onset type 1 diabetes influenza vaccination.
Giving children with type 1 diabetes influenza vaccination is completely harmless, but it may provide massive health benefits in addition to protecting against influenza.
The hope behind the new trial is that influenza vaccination may be immunomodulatory for the children, which could slow down the immune system’s destruction of the insulin-producing beta cells in the pancreas.
If influenza vaccination can slow down this destruction, the children might retain residual insulin production. This might help them control blood glucose better and, all other things being equal, will give the children a better prognosis.
“We think that influenza vaccination may provide cytokine modulation, which improves the immune response and may preserve beta cell function. We do not yet know how strong this effect will be, but we hope to be able to slow down the decline in beta cell function,” says Mads Fuglsang Kjølby.
He elaborates that the researchers are also examining blood samples from the children to study the effect of influenza vaccination in more detail.
“We are investigating the many cytokines to determine any possible effect there. This will provide mechanistic insight into the link between vaccination and a potential protective effect counteracting the destruction of the beta cells, and we can use this to design new studies with treatments for type 1 diabetes,” concludes Mads Fuglsang Kjølby.
