» Articles » PMID: 7574928

Major Injury Leads to Predominance of the T Helper-2 Lymphocyte Phenotype and Diminished Interleukin-12 Production Associated with Decreased Resistance to Infection

Overview
Journal Ann Surg
Specialty General Surgery
Date 1995 Oct 1
PMID 7574928
Citations 127
Authors
Affiliations
Soon will be listed here.
Abstract

Objective: Patients with serious traumatic injury and major burns and an animal model of burn injury were studied to determine the effect of injury on the production of cytokines typical of the T helper-2 lymphocyte phenotype as opposed to the T helper-1 phenotype and on the production of interleukin-12.

Summary Background Data: Perturbations of natural and adoptive immunity are related to the increased susceptibility to infection manifested by seriously injured and burn patients. Earlier work has shown that impaired adoptive immunity after injury is characterized by diminished production of interleukin-2 (IL-2), a product of Th lymphocytes. Exposure of naive Th cells to certain antigens and cytokines causes conversion to either the Th-1 or the Th-2 phenotype. Th-1 cells produce IL-2 and interferon-gamma (IFN-tau) and initiate cellular immunity. Th-2 cells secrete interleukin-4 (IL-4) and interleukin-10 (IL-10) and stimulate production of certain antibodies. Conversion to the Th-1 phenotype is facilitated by IL-12, and conversion to the Th-2 phenotype is promoted by IL-4. The authors believed that serious injury might cause conversion of Th cells to the Th-2 as opposed to the Th-1 phenotype rather than generalized Th suppression.

Methods: The authors studied circulating peripheral blood mononuclear cells (PBMC) from 16 major burn and 8 trauma patients on 32 occasions early after injury and from 13 age- and sex-matched healthy individuals for cytokine production after phytohemagglutinin stimulation. Also studied was a mouse model of 20% burn injury known to mimic the immune abnormalities seen in humans with burns. Splenocytes from burn mice, 10 to 12 per group, were studied after activation by concanavalin A or by the bacterial antigen Staphylococcus aureus Cowan strain I for cytokine production and cytokine messenger RNA expression as determined by reverse transcriptase polymerase chain reaction. Burn mice were compared with sham-burn controls and attention was focused on day 10 after burn injury, a time when IL-2 production and resistance to infection are highly suppressed. Finally, burn and sham-burn animals, 20 per group, were treated in vivo with IL-12 (25 ng daily for 5 days) and observed for mortality after septic challenge (cecal ligation and puncture [CLP]) performed on day 10 after injury.

Results: Peripheral blood mononuclear cells from burn and trauma patients produced less IFN-tau, the index cytokine of Th-1 cells, than PBMCs from healthy individuals 1 to 14 days after burn injury (SE = 77.6 +/- 16 pg/mL patients vs. 141.3 +/- 35 pg/mL controls, p < 0.05). However, production of IL-4, the index cytokine of Th-2 cells, by patient PBMCs was increased (51.0 +/- 13.0 pg/mL patients vs. 26.9 +/- 2.5 controls, p < 0.05). Splenocytes from mice 10 days after burn injury, when compared with sham-burn controls, showed diminished production of IL-2 (1.04 +/- 0.91 units/mL burns vs. 5.8 +/- 0.55 units/mL controls, p < 0.05) and IFN-tau (1.05 +/- 0.7 units/mL burns vs. 12.0 +/- 8.9 units/mL controls, p < 0.05). However, burn splenocytes produced more IL-4 (2492 +/- 157.0 pg/mL burns vs. 672.0 +/- 22.7 pg/mL controls, p < 0.01) and IL-10 (695.2 +/- 20.8 pg/mL burns vs. 567.0 +/- 16.7 pg/mL controls, p < 0.05). Splenocyte production of IL-12 was also reduced after burn (0.20 +/- 0.035 units/mL) as compared with sham burn (0.46 +/- 0.08 units/mL, p < 0.05). The reduction in IL-2, IFN-tau, and IL-12 production by burn splenocytes was reflected by a tenfold decrease in expression of their respective cytokine mRNAs. In vivo IL-12 treatment of burn animals decreased mortality from CLP on day 10 after injury from 85% to 15% (sham-burn mortality after CLP, 15%, p < 0.05) and increased splenocyte IFN-tau production to supranormal levels.

Conclusions: Serious injury induced diminished production of IL-1 2 and a shift to the Th-2 phenotype with increased production of IL-4 and IL-10, cytokines known to inhibit Th-1 function. The ability of exogenous IL-12 to restore Th-1 cytokine production and resistance to infection suggests a therapeutic role for IL-12 in the immune dysfunction seen after major injury.

Citing Articles

Development and validation of a mouse model to investigate post surgical pain after laparotomy.

Martinez J, Maisey T, Ingram N, Kapur N, Beales P, Jayne D Surg Open Sci. 2024; 20:106-115.

PMID: 39021615 PMC: 11253691. DOI: 10.1016/j.sopen.2024.06.002.


Digital twin mathematical models suggest individualized hemorrhagic shock resuscitation strategies.

Cannon J, Gruen D, Zamora R, Brostoff N, Hurst K, Harn J Commun Med (Lond). 2024; 4(1):113.

PMID: 38867000 PMC: 11169363. DOI: 10.1038/s43856-024-00535-6.


The Surgical Stress Response and Anesthesia: A Narrative Review.

Ivascu R, Torsin L, Hostiuc L, Nitipir C, Corneci D, Dutu M J Clin Med. 2024; 13(10).

PMID: 38792558 PMC: 11121777. DOI: 10.3390/jcm13103017.


Energy Expenditure, a New Tool for Monitoring Surgical Stress in Colorectal Oncological Patients: A Prospective, Monocentric Study.

Ivascu R, Dutu M, Corneci D, Nitipir C Cureus. 2024; 16(3):e56822.

PMID: 38654802 PMC: 11037290. DOI: 10.7759/cureus.56822.


Spatiotemporal orchestration of macrophage activation trajectories by Vγ4 T cells during skin wound healing.

Hu W, Zhang X, Liu Z, Yang J, Sheng H, Liu Z iScience. 2024; 27(4):109545.

PMID: 38617557 PMC: 11015460. DOI: 10.1016/j.isci.2024.109545.


References
1.
Gillis S, Ferm M, Ou W, Smith K . T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978; 120(6):2027-32. View

2.
Ayala A, Lehman D, Herdon C, Chaudry I . Mechanism of enhanced susceptibility to sepsis following hemorrhage. Interleukin-10 suppression of T-cell response is mediated by eicosanoid-induced interleukin-4 release. Arch Surg. 1994; 129(11):1172-8. DOI: 10.1001/archsurg.1994.01420350070009. View

3.
Wood J, Rodrick M, OMahony J, Palder S, Saporoschetz I, DEon P . Inadequate interleukin 2 production. A fundamental immunological deficiency in patients with major burns. Ann Surg. 1984; 200(3):311-20. PMC: 1250477. DOI: 10.1097/00000658-198409000-00008. View

4.
Cherwinski H, Schumacher J, Brown K, Mosmann T . Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987; 166(5):1229-44. PMC: 2189643. DOI: 10.1084/jem.166.5.1229. View

5.
Faist E, Mewes A, Strasser T, Walz A, Alkan S, Baker C . Alteration of monocyte function following major injury. Arch Surg. 1988; 123(3):287-92. DOI: 10.1001/archsurg.1988.01400270021002. View