Associations between Th1-related cytokines and complicated pediatric appendicitis.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
26 Feb 2024
Historique:
received: 18 07 2023
accepted: 05 02 2024
medline: 27 2 2024
pubmed: 27 2 2024
entrez: 26 2 2024
Statut: epublish

Résumé

The pathogenesis of appendicitis is not understood fully, and the diagnosis can be challenging. Previous research has suggested an association between a T helper (Th) 1-dependent immune response and complicated appendicitis. This prospective cohort study aimed to evaluate the association between serum concentrations of the Th1-associated cytokines interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-10, IL-17A and tumor necrosis factor beta (TNF-β) and the risk of complicated appendicitis in children. Appendicitis severity was determined through histopathological examination. A total of 137 children < 15 years with appendicitis were included with a median age of 10 years (IQR 8-12); 86 (63%) were boys, and 58 (42%) had complicated appendicitis. Children with complicated appendicitis had significantly higher concentrations of serum IL-6 and IL-10, and lower of TNF-β. After adjustment for age, symptom duration, and presence of appendicolith in a multivariable logistic regression, a higher concentration of IL-6 remained associated with an increased risk of complicated appendicitis (aOR 1.001 [95% CI 1.000-1.002], p = 0.02). Serum concentrations of IL-1α, IL-1β, IL-2, IL-10, IL-17A and TNF-β were not significantly associated with the risk of complicated appendicitis. In conclusion, our results suggests that the systemic inflammatory response in complicated appendicitis is complex and not solely Th1-dependent.

Identifiants

pubmed: 38409170
doi: 10.1038/s41598-024-53756-z
pii: 10.1038/s41598-024-53756-z
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

4613

Informations de copyright

© 2024. The Author(s).

Références

Scholer, S. J., Pituch, K., Orr, D. P. & Dittus, R. S. Clinical outcomes of children with acute abdominal pain. Pediatrics 98, 680–685 (1996).
doi: 10.1542/peds.98.4.680 pubmed: 8885946
Carr, N. J. The pathology of acute appendicitis. Ann. Diagn. Pathol. 4, 46–58 (2000).
doi: 10.1016/S1092-9134(00)90011-X pubmed: 10684382
Andersson, R. E. The natural history and traditional management of appendicitis revisited: Spontaneous resolution and predominance of prehospital perforations imply that a correct diagnosis is more important than an early diagnosis. World J. Surg. 31, 86–92 (2007).
doi: 10.1007/s00268-006-0056-y pubmed: 17180556
Andersson, R., Hugander, A., Thulin, A., Nyström, P. O. & Olaison, G. Indications for operation in suspected appendicitis and incidence of perforation. BMJ 308, 107–110 (1994).
doi: 10.1136/bmj.308.6921.107 pubmed: 8298378 pmcid: 2539237
Livingston, E. H., Woodward, W. A., Sarosi, G. A. & Haley, R. W. Disconnect between incidence of nonperforated and perforated appendicitis: Implications for pathophysiology and management. Ann. Surg. 245, 886–892 (2007).
doi: 10.1097/01.sla.0000256391.05233.aa pubmed: 17522514 pmcid: 1876946
Moltubak, E., Landerholm, K., Blomberg, M., Redéen, S. & Andersson, R. E. Major variation in the incidence of appendicitis before, during and after pregnancy: A population-based cohort study. World J. Surg. 44, 2601–2608 (2020).
doi: 10.1007/s00268-020-05524-z pubmed: 32328784
Nyboe Andersen, N., Gørtz, S., Frisch, M. & Jess, T. Reduced risk of UC in families affected by appendicitis: A Danish national cohort study. Gut 66, 1398–1402 (2017).
doi: 10.1136/gutjnl-2015-311131 pubmed: 27196591
Andersson, R. E., Olaison, G., Tysk, C. & Ekbom, A. Appendectomy is followed by increased risk of Crohn’s disease. Gastroenterology 124, 40–46 (2003).
doi: 10.1053/gast.2003.50021 pubmed: 12512028
Rubér, M. et al. Systemic Th17-like cytokine pattern in gangrenous appendicitis but not in phlegmonous appendicitis. Surgery 147, 366–372 (2010).
doi: 10.1016/j.surg.2009.09.039 pubmed: 19892382
Dimberg, J., Rubér, M., Skarstedt, M., Andersson, M. & Andersson, R. E. Genetic polymorphism patterns suggest a genetic driven inflammatory response as pathogenesis in appendicitis. Int. J. Colorectal. Dis. 35, 277–284 (2020).
doi: 10.1007/s00384-019-03473-1 pubmed: 31845023
Omling, E. et al. Nationwide paediatric cohort study of a protective association between allergy and complicated appendicitis. Br. J. Surg. 108, 1491–1497 (2021).
doi: 10.1093/bjs/znab326 pubmed: 34689186 pmcid: 10364888
Salö, M., Gudjonsdottir, J., Omling, E., Hagander, L. & Stenström, P. Association of IgE-mediated allergy with risk of complicated appendicitis in a pediatric population. JAMA Pediatr. 172, 943–948 (2018).
doi: 10.1001/jamapediatrics.2018.1634 pubmed: 30083704 pmcid: 6233766
Gudjonsdottir, J. et al. An evaluation of serum IgE and Th2-associated interleukins in children with uncomplicated and complicated appendicitis. Front Pediatr 10, 884138 (2022).
doi: 10.3389/fped.2022.884138 pubmed: 35586830 pmcid: 9108389
Arredondo Montero, J. et al. Diagnostic performance of serum interleukin-6 in pediatric acute appendicitis: A systematic review. World J. Pediatr. 18, 91–99 (2022).
doi: 10.1007/s12519-021-00488-z pubmed: 34978051
Stankovic, N. et al. Possible cytokine biomarkers in pediatric acute appendicitis. Ital. J. Pediatr. 45, 125 (2019).
doi: 10.1186/s13052-019-0726-7 pubmed: 31615548 pmcid: 6794741
Yoon, D. Y. et al. Human cytokine levels in nonperforated versus perforated appendicitis: Molecular serum markers for extent of disease?. Am. Surg. 68, 1033–1037 (2002).
doi: 10.1177/000313480206801201 pubmed: 12516803
Binboga, S. et al. Diagnostic value of serum cytokines in predicting a complicated acute appendicitis. An. Acad. Bras. Cienc. 94, e20201947 (2022).
doi: 10.1590/0001-3765202220201947 pubmed: 35507979
Maita, S., Andersson, B., Svensson, J. F. & Wester, T. Nonoperative treatment for nonperforated appendicitis in children: A systematic review and meta-analysis. Pediatr. Surg. Int. 36, 261–269 (2020).
doi: 10.1007/s00383-019-04610-1 pubmed: 31838546
Omling, E. et al. A nationwide cohort study of outcome after pediatric appendicitis. Eur. J. Pediatr. Surg. 31, 191–198 (2021).
doi: 10.1055/s-0040-1712508 pubmed: 32590867
Håkanson, C. A., Fredriksson, F. & Lilja, H. E. Adhesive small bowel obstruction after appendectomy in children—laparoscopic versus open approach. J. Pediatr. Surg. 55, 2419–2424 (2020).
doi: 10.1016/j.jpedsurg.2020.02.024 pubmed: 32192735
Rawolle, T. et al. Sonographic differentiation of complicated from uncomplicated appendicitis. Br. J. Radiol. 92, 20190102 (2019).
doi: 10.1259/bjr.20190102 pubmed: 31112397 pmcid: 6636276
Tong, L. et al. The utility of sonographic signs to diagnose simple and complicated appendicitis in children. Pediatr. Surg. Int. 39, 114 (2023).
doi: 10.1007/s00383-023-05397-y pubmed: 36764977 pmcid: 9918567
Fraser, J. D. et al. Accuracy of computed tomography in predicting appendiceal perforation. J. Pediatr. Surg. 45, 231–234 (2010) (discussion 234–234).
doi: 10.1016/j.jpedsurg.2009.10.040 pubmed: 20105609
Miglioretti, D. L. et al. The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk. JAMA Pediatr. 167, 700–707 (2013).
doi: 10.1001/jamapediatrics.2013.311 pubmed: 23754213 pmcid: 3936795
Brenner, D., Elliston, C., Hall, E. & Berdon, W. Estimated risks of radiation-induced fatal cancer from pediatric CT. Am. J. Roentgenol. 176, 289–296 (2001).
doi: 10.2214/ajr.176.2.1760289
Cameron, D. B. et al. Development and implications of an evidence-based and public health-relevant definition of complicated appendicitis in children. Ann. Surg. 271, 962–968 (2020).
doi: 10.1097/SLA.0000000000003059 pubmed: 30308607
St Peter, S. D., Sharp, S. W., Holcomb, G. W. & Ostlie, D. J. An evidence-based definition for perforated appendicitis derived from a prospective randomized trial. J. Pediatr. Surg. 43, 2242–2245 (2008).
doi: 10.1016/j.jpedsurg.2008.08.051 pubmed: 19040944
Di Mitri, M. et al. IL-6 serum levels can enhance the diagnostic power of standard blood tests for acute appendicitis. Child. (Basel) 9, 1425 (2022).
Arredondo Montero, J. et al. Discriminatory capacity of serum interleukin-6 between complicated and uncomplicated acute appendicitis in children: A prospective validation study. World J. Pediatr. 18, 810–817 (2022).
doi: 10.1007/s12519-022-00598-2 pubmed: 36114365 pmcid: 9617836
Kakar, M. et al. Determining acute complicated and uncomplicated appendicitis using serum and urine biomarkers: Interleukin-6 and neutrophil gelatinase-associated lipocalin. Pediatr. Surg. Int 36, 629–636 (2020).
doi: 10.1007/s00383-020-04650-y pubmed: 32219562
Castell, J. V. et al. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett. 242, 237–239 (1989).
doi: 10.1016/0014-5793(89)80476-4 pubmed: 2464504
Tanaka, T., Narazaki, M. & Kishimoto, T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb. Perspect. Biol. 6, a016295 (2014).
doi: 10.1101/cshperspect.a016295 pubmed: 25190079 pmcid: 4176007
Berka, I., Korček, P. & Straňák, Z. C-reactive protein, interleukin-6, and procalcitonin in diagnosis of late-onset bloodstream infection in very preterm infants. J. Pediatr. Infect. Dis. Soc. 10, 1004–1008 (2021).
Song, J. et al. Diagnostic and prognostic value of interleukin-6, pentraxin 3, and procalcitonin levels among sepsis and septic shock patients: A prospective controlled study according to the Sepsis-3 definitions. BMC Infect. Dis. 19, 968 (2019).
doi: 10.1186/s12879-019-4618-7 pubmed: 31718563 pmcid: 6852730
Rivera-Chavez, F. A., Wheeler, H., Lindberg, G., Munford, R. S. & O’Keefe, G. E. Regional and systemic cytokine responses to acute inflammation of the vermiform appendix. Ann. Surg. 237, 408–416 (2003).
doi: 10.1097/01.SLA.0000055274.56407.71 pubmed: 12616126 pmcid: 1514319
Saraiva, M. & O’Garra, A. The regulation of IL-10 production by immune cells. Nat. Rev. Immunol. 10, 170–181 (2010).
doi: 10.1038/nri2711 pubmed: 20154735
Ygberg, S. & Nilsson, A. The developing immune system—from foetus to toddler. Acta Paediatr. 101, 120–127 (2012).
doi: 10.1111/j.1651-2227.2011.02494.x pubmed: 22003882

Auteurs

Matilda Elliver (M)

Department of Clinical Sciences in Lund, Lund University, Lund, Sweden. matilda.elliver@med.lu.se.

Martin Salö (M)

Department of Clinical Sciences in Lund, Lund University, Lund, Sweden.
Department of Pediatric Surgery, Skåne University Hospital, Lund, Sweden.

Bodil Roth (B)

Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.
Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.

Bodil Ohlsson (B)

Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden.
Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.

Lars Hagander (L)

Department of Clinical Sciences in Lund, Lund University, Lund, Sweden.
Department of Pediatric Surgery, Skåne University Hospital, Lund, Sweden.

Johanna Gudjonsdottir (J)

Department of Clinical Sciences in Lund, Lund University, Lund, Sweden.
Department of Surgery, Skåne University Hospital, Malmö, Sweden.

Classifications MeSH