Perinatal brain injury is an important clinical and socioeconomic entity. It is a syndrome of impaired brain function in the early days of life, and it is a consequence of inadequate brain oxygenation before, during or shortly after birth, with high mortality rates and early and late morbidity rates.

Biological cells are sensitive to both pathological and non-pathological stress, which can activate the innate immune response. This activation often involves the release of heat shock proteins (HSPs), such as HSPA1A and HSPB1. However, the implications and relationships between HSP release and immune system activation remain unclear. While evidence suggests that HSPs play a role in immune system activation and regulation, their immune regulatory characteristics are still debated.

The modulation of the innate immune system has been a significant area of interest in research, as it represents the body’s first line of defense against pathogens. Heat shock proteins (HSPs), particularly small HSP, like HSPB1 (HSP27), are emerging as potent therapeutic options for preventing and managing inflammatory conditions due to their ability to modulate the immune system. 

Heat shock proteins (HSPs) are ubiquitous proteins that play an important role in cellular stress responses, contributing to immune activation through interactions with toll-like receptors (TLRs) and other pattern recognition receptors. Despite extensive research, the exact mechanism by which HSPs modulate immune responses is still unclear. This study explores the immune-modulatory role of HSPA1A by examining its effect on cytokine production in PMA-differentiated THP-1 macrophages, preincubated with TLR-specific blocking peptides prior to exposure to recombinant HSPA1A.