# Uncomplicated and Complicated Acute Appendicitis Induce Different Cytokine Patterns

**Authors:** Tatu Han, Tuomas Borman, Sanja Vanhatalo, Leo Lahti, Eliisa Löyttyniemi, Saija Hurme, Eveliina Munukka, Teemu Kallonen, Antti Hakanen, Maija Hollmén, Paulina Salminen

PMC · DOI: 10.1111/apm.70168 · Apmis · 2026-02-19

## TL;DR

The study found that different types of acute appendicitis trigger distinct immune responses, with IL-6 being a potential marker for severe cases.

## Contribution

The research identifies unique cytokine profiles for uncomplicated and complicated appendicitis, suggesting IL-6 as a diagnostic biomarker.

## Key findings

- Complicated appendicitis shows significantly higher levels of IL-6, HGF, and MCP-1 compared to uncomplicated cases.
- IL-6 has the best diagnostic performance (AUC 0.785) for predicting complicated appendicitis.
- The immune response differs between uncomplicated and complicated appendicitis, indicating distinct disease mechanisms.

## Abstract

Although acute appendicitis is one of the most common reasons for emergency surgery, the immunopathogenesis of appendicitis is unclear. The aim of this prospective pre‐defined subgroup analysis study was to characterize serum cytokine profiles and their diagnostic potential in distinguishing between appendicitis severity to offer further insight into the immunopathology of appendicitis. We analyzed 48 cytokines from the serum samples of patients with either uncomplicated or complicated appendicitis. Out of the 113 patients included in the study, 72 patients presented with uncomplicated and 41 patients with complicated acute appendicitis. Compared to uncomplicated appendicitis, complicated appendicitis showed statistically significantly elevated levels in interleukin 6 (IL‐6) (p < 0.001), hepatocyte growth factor (HGF) (p = 0.003), and monocyte chemoattractant protein 1 (MCP‐1) (p < 0.001). IL‐6 had the best performance (area under curve 0.785) in predicting complicated acute appendicitis. The immune response is notably different between complicated and uncomplicated appendicitis, underlining the two different diseases within acute appendicitis. IL‐6 may be utilized as a diagnostic biomarker for complicated appendicitis.

Trial Registration:
Clinicaltrials.gov NCT03257423

## Linked entities

- **Proteins:** IL6 (interleukin 6), HGF (hepatocyte growth factor), CCL2 (C-C motif chemokine ligand 2)
- **Diseases:** acute appendicitis (MONDO:0005649)

## Full-text entities

- **Genes:** HGF (hepatocyte growth factor) [NCBI Gene 3082] {aka DFNB39, F-TCF, HGFB, HPTA, SF}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** TB (MESH:D014390), fever (MESH:D005334), gangrene (MESH:D005734), Uncomplicated (MESH:C536333), bacterial infection (MESH:D001424), perforation (MESH:D057112), allergy (MESH:D004342), infection (MESH:D007239), tumor (MESH:D009369), abdominal pain (MESH:D015746), edema (MESH:D004487), abscess (MESH:D000038), inflammation (MESH:D007249), Complicated (MESH:D008107), APPendicitis (MESH:D001064)
- **Species:** Bacteroides fragilis (species) [taxon 817], Homo sapiens (human, species) [taxon 9606], Escherichia coli (E. coli, species) [taxon 562]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12917868/full.md

## References

51 references — full list in the complete paper: https://tomesphere.com/paper/PMC12917868/full.md

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Source: https://tomesphere.com/paper/PMC12917868