**9. Conclusion**

anti-tumour ability [87, 159–161]. In the inflammation environment, the amounts of M1 and M2 macrophages are not equal [162]. The tumour environment contains vast quantities of transmitters such as M-CSF, IL-6, IL-10, TGF-β and COX-2 that induce tumour megakaryocytes to differentiate into M2 macrophages, which, in addition to having inferior antigen-presenting and cytotoxic abilities, also secrete factors that inhibit immune cells, resulting in enhanced immune inhibitory effects in the tumour environment [49, 98, 102–104, 109–114]. M2 macrophages in tumour bearing mice enhance tumour growth and immune inhibitory effects. They also secrete cytokines, such as IL-10 and TGF-β, in high quantities, which attract non-cytotoxic Treg cells and TH2 cells to congregate in tumour tissue; those cells inhibit the differentiation and normal function of T cells, including their cytotoxic ability, and further promote T-cell apoptosis [49, 98, 115, 163, 164]. The polarisation of TH1 and TH2 is built on cytokine patterns; polarisation begins when the antigen-presenting cells interact with naive T cells; they polarise into Type 1 (TH1) and TH2 cells in response to the type of antigen encountered [165]. TH1 and TH2 cells secrete different cytokines; TH1 cells rely on IL-2, IFN-γ and TNF, which are involved in cell-mediated immunity against pathogens, but TH2 cells depend mostly on IL-4 and IL-5, which stimulate the production of IgE antibodies and eosinophil responses, resulting in allergic diseases [166, 167]. Although an imbalanced TH1/TH2 immune response is linked to certain hypersensitivity disorders such as allergies, asthma and hay fever [168], studies have suggested that using a biological response modifier to restore the balance between TH1 and TH2 immune response can be a potential treatment option for IgE-dependent hypersensitivity [169]. *Ganoderma lucidum* is a medicinal mushroom that has been widely used as a folk medicine in Asian countries such as China and Japan for hundreds of years for its immunomodulating and anti-tumour effects. Numerous biologically available substances with immunity enhancement effects, particularly polysaccharides, have been isolated from the

Anti-microbial peptides are effective components of innate immunity that exist widely in biological systems. One of the specific anti-microbial peptides, hepcidin, is a 25-amino acid antibiotic peptide synthesised in the liver. Hepcidin is responsible for regulating iron balance and recycling iron in humans and mice. Studies have reported 0–100 μg/ml concentrations of hepcidin incubated with HT1080, Hep-G2 and HeLa for 24 h. The results have indicated higher growth inhibition ratios after 70 μg/ml treatment with hepcidin in HT1080 cells; the treatment has been very effective in inhibiting the growth of fibrosarcoma cells [171, 172]. Tachyplesin is an anti-microbial peptide present in the leukocytes of the horseshoe crab (*Tachypleus tridenta‐ tus*); it inhibited the growth of TSU tumour cells on the CAM of chicken embryos as well as the growth of B16 tumour cells in syngenic mice; moreover, it blocked the proliferation of both tumour and endothelial cells in culture in a dose-dependent manner, whereas proliferation was relatively unaffected in non-tumourigenic cell lines Cos-7 and NIH-3T3 [173]. D-K4R2L9 is a peptide comprised of Leu, Lys and Arg residues, totalling 15 amino acid residues that bind to and lyse B16-F10 mouse melanoma cells in culture at concentrations that do not harm normal 3T3 fibroblasts or erythrocytes; this can be conducted to prevent intravenous-injected D122 lung carcinoma cells from forming lung tumours in mice [174, 175]. Bovine lactoferricin (LfcinB), an anti-microbial peptide, is a 25-amino acid long highly basic peptide with a disulfide bridge between two cysteines, thus giving it a cyclic twisted anti-parallel β-sheet solution

extract of *G. lucidum* [170].

178 Wound Healing - New insights into Ancient Challenges

From the injury to the wound recovery, there are a series of physiological responses that occur in relation to immune cells. Polarisation of the macrophage is an important response in wound healing. A series of inflammatory factors are cited having notable function in the differentiation from novel macrophage into the classical macrophage (M1). The cellular mechanism involved in the regulation of classical macrophage (M1) and alternative macrophage (M2) was documented in the wound healing process. At the present time, the M1/M2 differentiation was studied for selected immune responses. However, future studies may allow possible therapeutic targets considering this process in wound healing.

The immunotherapy that is being developed offers some advantageous immunomodulation factors that are known in the field of alternative medicine, such as mushroom beta-glucan, anti-microbial peptides and triterpenoid; these factors represent a novel therapeutic approach for anti-inflammation. These factors may be a viable alternative approach to the problem of drug resistance. Recent insights into wound healing and anti-inflammation are promising; however, exploiting these insights is complex because it involves chemistry, biology, instrumentation science and formulation science. Discovering new methods that are more effective in targets is difficult. Immunotherapy might be an alternative therapy that can be applied in the early phases of clinical therapy. Similarly, immunomodulation might be applicable in the early phases of immune disease.
