Journal of Surgery

Introduction

Posttraumatic dystrophy remains an unresolved therapeutic problem. Recently the origin of this complication was deduced on damage associated molecular patterns DAMPs, which are formed during tissue trauma from cellular fragments and humoral processes. From the beginning the innate immunity reacts on these “foreign” self molecules with activation of cells and cytokines. Phagocytosis by antigen presenting cells APC provides a strong control of detritus to detect invaders and prevent dangers for the host (Figure 1). Normally posttraumatic inflammatory reaction is aseptic and healing is reached in two to three weeks. In this period the detritus should be absorbed and the local homeostasis restored. Any disorder like hypoxia provokes the activation of local transient receptor potentials, acidosis by free radicals and cellular response. The innate immunity response persists with local perpetuation of vicious circles of aseptic inflammatory reactions. Representative cells for such reactions are the lymphocytes and especially the ubiquitous tissue homing natural killing T cells NKT.  Owing their plasticity in different tissues they imply divers T cell receptors and are therefore named dNKT cells. They are self propagating and stimulate the building of neutrophils and B-cells beside extrusion of cytokine storm (Table 1).

Taking together the conclusion is to use lymphotoxic drugs to suppress lymphocytes in case of prolonged posttraumatic aseptic inflammatory reaction with clinical signs and symptoms locally around the trauma region.

Materials and Methods

For the first time nine consecutive out-patients with traumata of upper extremity or foot were treated because of persistent pain and restricted functionality of the traumatized extremity. Further details are provided in Table 3, the reader is requested to see there. As usual, venous oxygen pressure was high on the affected limb and lower on contralateral side [2,3]. Referring therapy there are several international communications [4,5], which recommend the use of GC generally in the case of perpetual inflammatory reactions. Different diagnoses from distinct clinical departments make it difficult to transfer this recommendation to Posttraumatic Dystrophy where damage of tissues triggers the inflammation. It is notable that most patients were affected by healthy conditions. Furthermore the aseptic posttraumatic inflammatory reactions are locally developed and maintained by innate immunity. Therefore the effectors of dNKT cells (Table 1) [6] were compared with the specific efficacy of GC analyzed in three pharmacological publications [7-10] (Table 2A and Table 2B). Nearly all cytokines and chemokines of dNKT effectors were blocked also the transcription factor iNOS, cellular immune response, T cell development and antigene presentation. Further transcription factors of the cytosolic pathway are suppressed and prevent the transcription of proinflammatory cytokines [10]. These results encouraged to use GC in posttraumatic patients with chronification of innate inflammatory reactions and typical PTD history (8 to 13 weeks of aggravation), clinical signs and symptoms (Table 3).

Table 3: Patients: Nine consecutive patients with prolonged aseptic inflammatory reactions after traumatic incidence of the arm or foot were treated in the trauma department of affiliated Hospital of Medical School of University of Ulm in Immenstadt/Allgäu, Bavaria, Germany, leader Dr. A. Scola.

Table 2A

Table 2B

Table 2A and 2B: Comparison of activated dNKT cell effectors (red column, signs and terms,[6]) and their suppression by glucocorticoides (black column, signs and terms) with three pharmacologic articles 1: Czock 2005 [9], 2: Shimba 2020 [7,8], 3: Taves 2021 [10]. The majority of the activated dNKT cell effectors (25/29) are inhibited, only four cytokines out of 23 (indicated as ü: IL-10, IL-17, IL-21 and TGFβ) are not suppressed directly but indirectly reduced by impaired production of T helper cells. Coincidences are indicated as ü.. However, the activity of GC encompasses a large range of additional proinflammatory effectors (examples indicated as ü).

(Abrivation: PAPC 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphatidylcholine, LDL low density lipoprotein, RNS reactive nitrogen species, ROS reactive oxygen species, TLR toll-like receptor, CD cluster of differentiation)

Figure 1: (mod. based on  [11] ): Schematic presentation of activation of dNKT cell through antigene presenting dendritic cell activated T cell receptor (weak) and strong IL receptor signal (IL-12, extruded form DC granules). Effectors see Table 3.

Table 1: Effectors of activated dNKT cell (cytokine storm) (6). Exocytosis starts about 30 min after activation due to innate microRNA of cytokins (INF-γ, IL-4) and lasts up to 2 days.