Clínic-IDIBAPS shows the effectiveness in mice of a new complementary therapy to treat sepsis

Sepsis is a territory in which there is a very long way to go, especially in terms of the benefit that new complementary strategies can bring to conventional antibiotic therapy. This has been pointed out by researchers from the IDIBAPS Immunoreceptors Group, in which Dr. Mario Martínez-Florensa, the first author of the study, and Dr. Francisco Lozano, team leader and Senior Consultant of the Immunology Service of the Hospital Clínic are members. His research, carried out for the time being in mice, has shown that the antibiotic Imipenem increases its efficacy when combined with the intravenous administration of the CD6 protein, a receptor present in the T lymphocytes of the immune system.

Sepsis is a systemic response caused by an infection leading to a sustained excessive inflammatory state over time. If left unresolved, it can lead to multi-organ dysfunction and, occasionally, death. The mortality rate is 35%, and in cases of septic shock, when the systemic response is accompanied by circulatory, cellular and metabolic abnormalities, it increases up to 60%.

Antibiotics are an indispensable part of their treatment, but they are insufficient to reduce completely the mortality associated with multiorgan dysfunction caused by this syndrome. Moreover, the increase of drug-resistant bacteria, makes the search for new complementary strategies to antibiotics something mandatory to researchers in order to find new ways to treat sepsis. “Antibiotics will always be incomplete“, Dr. Martinez-Florensa recalls, “especially,” adds Dr. Lozano, “because they do not act directly on the immflamatory reaction associated with the presence of circulating intact bacteria or their components“.

The research for new therapeutic alternatives led the Group of Immunoreceptors of the IDIBAPS to the CD6 molecule. “We had been working for a long time on this receptor because it is involved in the activation of the lymphocytes, the cells responsible for the immune response“, says Dr. Lozano. “After demonstrating its unsuspected interacting capacity with essential components of the bacterial walls, the next question“, he adds, “was whether this could serve to supplement antibiotics“.

A harmless molecule

Researchers have seen that CD6 acts by sticking to the inflammatory products that bacteria generate. Consequently, inflammation decreases and so do mortality. This is what they have been able to prove by inducing sepsis in mice and administering the molecule in soluble form together with antibiotics.

The other options for controlling the inflammation that carry the infections do not seem to be as effective as the CD6 protein. “It is a molecule of our own that is found in the T lymphocytes of our body, and therefore is innocuous. We are in the era of immunotherapy“, says Dr. Lozano. “Corticosteroids, used to control inflammation, cause immunosuppression that the CD6 molecule does not raise” he adds. In addition, this receptor is able to act on a wide range of bacteria. As Dr. Martinez Florensa says ”it is effective against those who are resistant to antibiotics“.

Now, the challenge of the team led by Dr. Lozano is to come up with a sustainable system that allows synthesizing the protein, since producing a human molecule on an industrial scale is very expensive. However, for the time being the European patent application has been initiated to cover this new combinatorial therapy in sepsis of bacterial origin.