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UCL-led research team has found that an anti-inflammatory pill could make vaccines more effective for elderly people. An excessive inflammation reaction in older people can obstruct the immune system. The immune system declines with age, and people can be affected by pathogens they were once immune to, when it comes to cutaneous immunity – specific to skin – the immune system was being obstructed by skin cells that were too prone to producing inflammation responses.
To investigate immune responses, the researchers injected an antigen – a derivative of a pathogen that creates an immune response without inducing illness – into the skin of 175 participants (78 were over 65 years old and the rest were under 40). The pathogen was the varicella zoster virus (VZV), which causes chicken pox. After a person contracts chicken pox, they become immune to VZV, but it can re-activate in old age and cause shingles if T cell immune responses aren’t strong enough.
All study participants had previously had chicken pox, meaning they should be immune. The researchers found that the older subjects exhibited weaker immune responses, as there was less T cell activation, and less reddening and swelling of the skin. The reduced response was not due to a lack of resident memory T cells present in the skin. As a control, they also injected a benign saline solution into the other arm of each participant.
The researchers noticed that even the saline solution brought about an inflammation response in some of the older participants. Those who had the strongest inflammation responses to the saline solution had the weakest immune responses to the VZV, suggesting that the excessive inflammation was inhibiting VZV-specific immunity. Normally inflammation is a healthy part of the body’s immune response, too much inflammation was getting in the way of the rest of the body’s defences.
By analysing skin biopsies post-injection, the researchers found that the excessive inflammation was associated with activation of the p38 MAP kinase pathway. To test whether this enzyme was to blame, they conducted a follow-up test with 18 of the over-65 participants, who took Losmapimod, a drug that inhibits the enzyme in order to reduce acute inflammation responses. While the drug was designed for long-term use and has been trialled for treatments of COPD and arthritis, the participants only took the pill for 4 days, before once again being injected with the VZV antigen. Losmapimod treatment successfully increased the immune responses to the VZV antigen.
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