Study shows TB drugs strengthen immunity

A study from Karolinska Institutet has shown that existing drugs used for treating tuberculosis (TB) can strengthen the immune system.

The study's results offer hope of a new treatment principle for infectious diseases that strengthens the effect of traditional antibiotic treatments and reduces the risk of developing a resistance.

Widespread resistance to antibiotics requires new, expensive medicines with various side-effects to be used against tubercle bacteria. However, many affected countries lack access to such medicines. Researchers are therefore trying to develop new strategies for effective treatment of TB, which continues to be a major worldwide problem.

The researchers behind the study are investigating how to activate the body's own antibiotics, antimicrobial peptides, which form a part of the innate immune defence system. The peptides are produced in all mucus membranes and also in granulocytes and macrophages, two types of white blood cells that are recruited to the site of infection.

“We have focused particularly on increasing the body's production of its own peptides with the help of existing drugs. LL-37, a human antimicrobial peptide that we discovered in 1995, is highly effective against TB bacteria,” said Birgitta Agerberth at the Department of Laboratory Medicine, Karolinska Institutet, one of the researchers who has led the study.

Researchers have already shown that the drugs vitamin D and phenylbutyrate increase the production of LL-37. They have now demonstrated that LL-37 plays a key role in the manner in which these drugs kill the TB bacteria. It is already known that vitamin D can trigger a process known as autophagy, which is important for killing pathogenic bacteria inside macrophages and other cells. In this study, researchers have shown that phenylbutyrate also activates autophagy and that vitamin D and phenylbutyrate work even more effectively when used in combination.

Another study from the same research group showed that supplementary treatment with phenylbutyrate and vitamin D had positive results when combined with standard antibiotics in the treatment of newly diagnosed TB patients in Dhaka, Bangladesh.

Agerberth added: “The results show that we can strengthen the body's defence against serious infections such as TB by increasing the production of antimicrobial peptides. Both these studies provide combined support for a new treatment principle for infectious diseases with the activation of the body's own defence system combined with traditional antibiotic treatments. This new treatment strategy, which we call host-directed therapy, has many advantages — it minimises the risk of developing resistance, it strengthens the effect of regular antibiotics and it controls the often damaging inflammation that occurs commonly in different infections."

The research is funded by the Swedish Foundation for Strategic Research, Swedish Heart-Lung Foundation, the Swedish Research Council and SIDA, among others.