IL-40 and IL-41 Levels in Sepsis, Septic Shock, and Healthy Individuals

Comparison of IL-40 and IL-41 Levels in Patients With Sepsis and Septic Shock to Healthy Individuals

This study aims to investigate the blood levels of two recently identified immune-related proteins, Interleukin-40 (IL-40) and Interleukin-41 (IL-41), in patients with sepsis and its more severe form, septic shock. Sepsis is a serious condition caused by an abnormal immune response to infection, which can lead to organ dysfunction. Septic shock represents an advanced stage of sepsis, characterized by significantly higher mortality risk.

IL-40 and IL-41 are newly discovered molecules that are thought to play important roles in the immune system. In this study, the blood concentrations of IL-40 and IL-41 in patients diagnosed with sepsis or septic shock will be measured and compared with those in healthy individuals. The findings may contribute to understanding whether these proteins can be used as biomarkers in the diagnosis or monitoring of treatment in sepsis-related conditions.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection and is evaluated by an increase of two or more points in the Sequential Organ Failure Assessment (SOFA) score. Septic shock is characterized by hypotension that persists despite adequate fluid resuscitation (mean arterial pressure ≤65 mmHg) and a serum lactate level greater than 2 mmol/L. Septic shock represents a more severe clinical condition, with mortality rates reaching up to 60%.

Interleukin-40 (IL-40) is a recently discovered pro-inflammatory cytokine encoded by the chromosome 17 open reading frame 99 (C17orf99) gene. It is primarily produced by bone marrow, fetal liver, and activated peripheral B cells. IL-40 plays an essential role in immunoglobulin A production, humoral immune regulation, and B cell development. It has also been implicated in the pathogenesis of inflammatory diseases such as rheumatoid arthritis.

Interleukin-41 (IL-41), also known as meteorin-like protein (Metrnl), was identified in 2004 and is encoded by the meteorin-like (METRNL) gene located on chromosome 17q25.3. IL-41 is an anti-inflammatory cytokine expressed in tissues such as the intestines, skin, respiratory tract, and central nervous system. It is secreted primarily by alternatively activated macrophages and M2-like macrophages and has roles in both innate and adaptive immune responses.

The roles of IL-40 and IL-41 in sepsis and septic shock have not yet been fully elucidated. Understanding the involvement of these novel cytokines in inflammatory processes may provide new insights into the diagnosis and treatment of critical conditions such as sepsis and septic shock. The aim of this study is to compare IL-40 and IL-41 levels in patients diagnosed with sepsis or septic shock to those of healthy individuals.

Inclusion Criteria:

• Patient Group:

Clinical diagnosis of sepsis or septic shock, based on validated diagnostic criteria (e.g., Sepsis-3)

Age 18 years or older

Ability and willingness to provide a blood sample prior to initiation of antibiotic treatment

Healthy Control Group:

Determined to be in good general health based on physical examination and medical history

Age 18 years or older

Willingness to provide written informed consent

Exclusion Criteria:

• Patient Group:

History of chronic inflammatory diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus)

Active cancer or current use of immunosuppressive therapy

Pregnant or breastfeeding

Presence of other serious conditions that may interfere with diagnosis or treatment (e.g., liver failure, chronic kidney disease)

Healthy Control Group:

Recent infection within the past month or use of antibiotics in the last 6 weeks

History of chronic inflammatory diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus)

Underwent surgery within the past 6 months

Conditions that may affect blood parameters, such as recent blood donation or intense physical activity

Pregnant or breastfeeding