Cytokines and growth factors

Why do some people fall seriously ill and die with Covid whilst others are asymptomatic? A remarkable characteristic of Covid-19 is the way it affects individuals so differently: Around 40% of people infected with SARS-CoV-2 are asymptomatic. A further 40% experience mild, upper respiratory tract symptoms. The remaining 20% develop pneumonia, of which 10% will become hypoxic, leading to critical illness in around 3%. In addition to age, sex and underlying health issues, the ability to deploy key immunomodulatory cytokines has emerged as an important risk factor for mortality.

The calorie-rich environment of the modern world is leading to poorer diets for many people. Excess calories contribute to inflammation throughout the body, early-onset of age-related diseases/mortality and a shorter life expectancy. Extreme calorie restriction, 50% below recommended daily limits, may increase lifespan beyond current levels. However, for many people, this is not a price worth paying. Can drugs allow us to achieve greater longevity without severe calorie restriction?

In a previous article about durotaxis, we discussed how cell movements can be guided by elasticity cues at the cell-substrate interface. Here, we focus on the process of cell migration following biochemical cues and the clinical benefits promised by this developing area of research.

The distinction between peptides and proteins is not always apparent, but it is important to understand. Peptides and proteins are, indeed, fundamentally the same, each being composed of amino acids held together by peptide bonds. However, fundamental differences between proteins and peptides go beyond an arbitrary length threshold. Look closer and they differ in structure, function, and therapeutic use.

The immune response is orchestrated. There are mechanisms to activate and deactivate activities. Myeloid-derived suppressor cells (MDSCs) are immune cells that act as regulators of immune responses. They are important in several diseases including tumor growth and the response to cancer therapies, Graft-Versus-Host Disease (GVHD), various autoimmune diseases, and COVID-19. Novel drugs developed to modulate MDSCs are showing promise with ongoing clinical trials for COVID-19 and some cancers.

Among the five classes of therapeutics, peptides represent a unique niche of pharmaceutical compounds within the protein class. The excitement surrounding peptide therapy arises from their distinct physical and biochemical features that present an opportunity for therapeutic intervention that can specifically target a wide range of cells and manipulate their response on a molecular level. However, challenges around their pharmacokinetics, notably poor stability have hampered more widespread use. Addressing these issues will release a new wave of drugs for urgent medical challenges such as anti-microbial resistance.

The effect of Covid on pregnant women is of great importance particularly in relation to the development of cytokine storms and the harmful effects these can have. A recent study published in Nature Immunology reported on maternal SARS-CoV2 infection and transmission of cytokines and antibodies to the neonate.

A healthy immune system is essential for defending against pathogens. However, it can also present as a liability rather than an asset. The greatest threat to survival in some of the most critical COVID-19 cases and other medical emergencies isn’t the infection itself, but rather an uncontrolled immune response to the infection that the human body sometimes generates. Understanding the genesis of a cytokine storm is key to developing strategies to prevent the immune system spiraling out of control.

Growing evidence regarding the side effects of currently available anti-inflammatory drugs (NSAIDs, antibiotics, etc.) and concerns around their appropriate role during cytokine storms has triggered a new era of innovation in the treatment of immune-mediated diseases. Owning to the ubiquitous nature and expanding role of cytokines in the various biological phenomena, anticytokine therapies have gained a leading role in this context.

Why COVID-19 pathogenesis varies so widely between different in SARS-CoV2 infected individuals has remained somewhat of a mystery. However, cytokines have served as a prognostic marker for COVID-19 disease course and outcome and their involvement is closely connected with the development of Long COVID.