Author(s): Luma Saleem Hachim, Ikbal Khudhur Aljoofy, Khawlah Jebur Khalaf, Sarah S. Abdul-Hussein

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DOI: 10.52711/0974-360X.2023.00143   

Address: Luma Saleem Hachim1, Ikbal Khudhur Aljoofy2, Khawlah Jebur Khalaf3, Sarah S. Abdul-Hussein
1,4Al-Kindy Teaching Hospital, Baghdad, Iraq.
2,3Department of Biology, College of Science, Mustansiriyah University, Baghdad, Iraq.
*Corresponding Author

Published In:   Volume - 16,      Issue - 2,     Year - 2023

This experimental in vivo purpose of this study was to look into the immunomodulatory effects of purified staphylokinase produced by local clinical Staphylococcus aureus isolates compared with streptokinase which is used as a thrombolytic agent. All mice (40) injected intramuscularly (i.m.) with different concentrations of the purified lyophilized staphylokinase and streptokinase for 12 days, and immunized with 10% SRBCs (i.p) on day 4 and 8 of the schedule, and Staphylococcus aureus suspension and normal saline for positive and negative control groups. Focus on the estimation of Arthus and delayed-type hypersensitivity with the absolute neutrophil count, measurement of antibody titter by Hemagglutination, and detecting serum concentration of cytokines (IL4 -IL10 -IL 17) and TLR-2 by using sandwich ELISA. The statistical analysis found a significant difference (P = 0.01) between staphylokinase and streptokinase treated groups and control groups (positive and negative). The data showed an increase in cytokine levels in treated groups compared with control groups. Observed in A2 (4µg staphylokinase) and B2 (4µg streptokinase)groups, also significant elevation (P = 0.01) of IL-10 level in all groups as compared to positive and negative control groups but the highest value was observed in A3 (8µg) and B3 (8µg) group. In conclusion, the staphylokinase is better than streptokinase because of the increasing level of IL-10 and less appearance of hypersensitivity, so decline in IL-4 and its small size, in addition, to act as an immunomodulator that indicates the possibility to use in the treatment of thrombosis.

Cite this article:
Luma Saleem Hachim, Ikbal Khudhur Aljoofy, Khawlah Jebur Khalaf, Sarah S. Abdul-Hussein. Immunomodulatory Activity of Staphylococcus aureus Purified Staphylokinase and Streptokinase in BALB/C mice. Research Journal of Pharmacy and Technology 2023; 16(2):839-7. doi: 10.52711/0974-360X.2023.00143

Luma Saleem Hachim, Ikbal Khudhur Aljoofy, Khawlah Jebur Khalaf, Sarah S. Abdul-Hussein. Immunomodulatory Activity of Staphylococcus aureus Purified Staphylokinase and Streptokinase in BALB/C mice. Research Journal of Pharmacy and Technology 2023; 16(2):839-7. doi: 10.52711/0974-360X.2023.00143   Available on:

1.    Kwieciński J, Josefsson E, Mitchell J, Higgins J, Magnusson M, et al. Activation of plasminogen by staphylokinase reduces the severity of Staphylococcus aureus systemic infection. The Journal of infectious diseases. 2010; 202(7): 1041-1049.‏
2.    Palande SV, Swamy DK. Study of antimicrobial activity of 2-[(1-Naphthalen-1-yl-ethylimino)-methyl]-phenol and its transition metal complexes on E.coli and Staphylococcus aureus.. Asian Journal of Research in Chemistry. 2018; 11(1):19-22. DOI:10.5958/0974-4150.2018.00005.6
3.    Sumera A, Chaudhury P, Haque S, Saha P, Paul D, Jawed A. Staphylokinase: A Potent Thrombolytic Agent.‏ Agent International Journal of Engineering Science Invention (IJESI). 2018; 7(1): 15-22.
4.    Sasmal A, Urolagin D. Immunomodulatory activity of Cestrum nocturnum. - A Comprehensive review. Asian Journal of Pharmacy and Technology. 2022; 12(1):33-37.  DOI: 10.52711/2231-5713.2022.00006
5.    Kwiecinski J, Jacobsson G, Karlsson M, Zhu X, Wang W, et al. Staphylokinase promotes the establishment of Staphylococcus aureus skin infections while decreasing disease severity. The Journal of infectious diseases, 2013; 208(6): 990-999.‏ doi: 10.1093/infdis/jit288.
6.    Al-Mosawi RAS, Al-Fartosi KG. Oxidant and Antioxidant Status of patients with Sickle cell –β Thalassemia in Thi-Qar Province, Iraq. Research Journal of Pharmacy and.Technology. 2020; 13(10):4796-4800. DOI: 10.5958/0974-360X.2020.00843.4
7.    Nguyen LT, Vogel HJ. Staphylokinase has distinct modes of interaction with antimicrobial peptides, modulating its plasminogen-activation properties. Scientific Reports, 2016; 6: 31817.
8.    Mohanasrinivasan V, Subathra DC, Dhanmoni K, Vaishnavi B, et al. Production and purification of staphylokinase from Staphylococcus hominis MSD1isolated from Kadi: A traditional Indian fermented food. International Journal of Pharmacy and Technology.  2015; 8(6): 265-272.
9.    Paswan. To assess the effectiveness of Self-Instructional Module (SIM) on knowledge regarding life style modification among Myocardial Infarction patients admitted in selected hospitals in Vidarbha Region.Asian Journal of Nursing Education and Research. 2018; 8(2): 247-267. DOI:10.5958/2349-2996.2018.00050.2
10.    Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. International Journal of Molecular Sciences. 2019; 20(23): 6008. doi: 10.3390/ijms20236008
11.    Kadhem SJ, Ali AK, AL_rikabi AN. Compartment Between Breast Cancer Patient Undergoing Chemotherapy and Healthy Women by Cytokinesis-block Micronucleus testand Nuclear Division Index. Research Journal of Pharmacy and Technology. 2018; 11(2):705-710. DOI:10.5958/0974-360X.2018.00133.6
12.    Jin W, Dong C. IL-17 cytokines in immunity and inflammation. Emerging Microbes and Infections. (2013); 2(1): 1-5.‏
13.    Iyer SS, Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Critical Reviews™ in Immunology. 2012; 32(1).‏ doi: 10.1615/critrevimmunol.v32.i1.30
14.    Gaidan AM,Abbas AA, Hassan MA, Hashim HM, Al-Mayah QS. The Impact of IL-10 C-597A Gene Polymorphisms on Asthma Susceptibility. Research Journal of Pharmacy and Technology. 2017; 10(9): 2867-2870. DOI: 10.5958/0974-360X.2017.00505.4
15.    de Oliviera NL, Massari P, Wetzler LM. The role of TLR2 in infection and immunity. Frontiers in Immunology, 2012; 2012; 3: 79.
16.    Ramesh A, Varma SR, Ramamurthy S, Al Shayeb M, Shahwan M, et al. Role of sToll-like receptors 2 and 4 in stage 2 periodontitis patients with and without type 2 diabetes: A Randomized clinical control trial. Research Journal of Pharmacy and Technology. 2021; 14(1): 397-404. DOI: 10.5958/0974-360X.2021.00072.X
17.    Tarek AE. Production of Staphylokinase from Locally Isolated Lysogenic Staphylococcus aureus. The Pharmaceutical and Chemical Journal, 2017; 4(1): 25-31.
18.    Hachim LS, Khalaf KJ, Aljoofy IK. Thrombolytic activity of purified staphylokinase produced from clinical isolates. International Journal of Drug Delivery Yechnology, 2020; 10(4): 571-576.
19.    Mageet AO, Abu Fanas AS, Shaheen IK, Hadi KMH, Abdelmagied MH. Variations of the Mesiodistal width of permanent teeth in a sample of patients attending Ajman University Dental College. Research Journal of Pharmacy and Technology. 2021; 14(12):6565-2. DOI: 10.52711/0974-360X.2021.01136
20.    Tansho S, Abe S, Mizutani S, Ono Y, Takesako K, Yamaguchi H. Protection of mice from lethal endogenous Candida albicans infection by immunization with Candida membrane antigen. Microbiology and immunology, 2002; 46(5): 307-311.‏
21.    Tefferi A, Hanson CA, Inwards DJ.  How to interpret and pursue an abnormal complete blood cell count in adults. In Mayo Clinic Proceedings, 2005; 80(7): 923-936. ‏
22.    Al-Joofy IKA. Studies on immunogenic properties of Rhizobium polysaccharide in Balbic mice. Msc Thesis College of science/ Al-Mustansiryah University:(1996).
23.    Mehra T, Agarwal I, Swami S. Ephemeral Marketing: Conceptualization and Measurement of its Effectiveness in Restaurant Industry. Asian Journal of Management. 2018; 9(1):87-91. DOI: 10.5958/2321-5763.2018.00013.6
24.    Froehlich H, Verma R. Arthus reaction to recombinant hepatitis B virus vaccine. Clinical Infectious Diseases, 2001; 33(6): 906-908.
25.    Krishnasamy L, SelvamM, Ravikrishnan B. Anticancer property of Colchicine isolated from Indigofera aspalathoids. Research Journal of Pharmacy and Technology. 2016; 9(4): 386-390. DOI:10.5958/0974-360X.2016.00069.X
26.    Dienz O, Eaton SM, Bond JP, Neveu W, Moquin D, et al. The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells. Journal of Experimental Medicine, 2009; 206(1): 69-78.‏
27.    Sivaraman T, Sreedevi NS, Meenatchisundaram S. Identification and Quantification of antivenom compounds from aqueous extract of Cyclea peltata root. Research Journal of Pharmacy and Technology. 2018; 11(4): 1386-1390. DOI: 10.5958/0974-360X.2018.00259.7
28.    Woo TM, Robinson MV. Pharmacotherapeutics for advanced practice nurse prescribers. FA Davis (2015).‏
29.    Gayathri M, Thenmozhi MS. Sex determination using Ramus Breadth and Bigonial Width of Mandible. Research Journal of Pharmacy. and Technology. 2015; 8(7): 923-926. DOI: 10.5958/0974-360X.2015.00152.3
30.    Justiz Vaillant AA, Vashisht R, Zito PM. Immediate Hypersensitivity Reactions. [Updated 2021 Nov 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
31.    Sacramento LA, da Costa JL, de Lima MH, Sampaio PA, Almeida RP, et al. Toll-like receptor 2 is required for inflammatory process development during Leishmaniainfantum infection. Frontiers in Microbiology, 2017; 8: 262.‏ doi: 10.3389/fmicb.2017.00262
32.    Page K, Lierl KM, Hughes VS, Zhou P, Ledford JR, Wills-Karp M. TLR2-mediated activation of neutrophils in response to German cockroach frass. The Journal of Immunology, 2008; 180(9): 6317-6324.‏
33.    Shah B, Burg N, Pillinger MH. Neutrophils. In Kelley and Firestein's textbook of rheumatology, (2017); 169-188. ‏
34.    Patra A, Chanda A, Mukherjee AK. Quantitative proteomic analysis of venom from Southern India common krait (Bungaruscaeruleus) and identification of poorly immunogenic toxins by immune-profiling against commercial antivenom. Expert Review of Proteomics, 2019; 16(5): 457-469.‏ doi: 10.1080/14789450.2019.1609945.
35.    de OlivieraNascimento L, Massari P, Wetzler LM. The role of TLR2 in infection and immunity. Frontiers in Immunology 2012; 3: 79.
36.    Warmerdam PA, Vanderlick K, Vandervoort P, De Smedt H, et al. Staphylokinase-specific cell-mediated immunity in humans. The Journal of Immunology, 2002; 168(1): 155-161.‏ doi: 10.4049/jimmunol.168.1.155.
37.    Parronchi P, de Carli M, Manetti R, Simonelli C, Piccinni MP, et al. Aberrant interleukin (IL)‐4 and IL‐5 production in vitro by CD4+ helper T cells from atopic subjects. European Journal of Immunology, 1992; 22(6): 1615-1620.‏
38.     Lee HS, Yule S, McKenzie A, Cross S, Reid T, Davidson R, Jennings K. Hypersensitivity reactions to streptokinase in patients with high pre-treatment antistreptokinase antibody and neutralisationtitres. European Heart Journal, 1993; 14(12): 1640-1643.‏
39.     Askarian F, Wagner T, Johannessen M, Nizet V. Staphylococcus aureus modulation of innate immune responses through Toll-like (TLR),(NOD)-like (NLR) and C-type lectin (CLR) receptors. FEMS Microbiology Reviews, 2018; 42(5): 656-671.‏ doi: 10.1093/femsre/fuy025.
40.    Jeon HY, Park JH, Park JI, Kim JY, Seo SM, et al. Cooperative interactions between Toll-like receptor 2 and Toll-like receptor 4 in murine Klebsiella pneumoniae infections. Journal of Microbiology and Biotechnology, 2017; 27: 1529-1538.‏ doi: 10.4014/jmb.1704.04039.
41.    Duthie MS, Windish HP, Fox CB, Reed SG. Use of defined TLR ligands as adjuvants within human vaccines. Immunological Reviews, 2011; 239(1): 178-196.‏
42.    Castell SD, Harman MF, Morón G, Maletto BA, Pistoresi-Palencia MC. Neutrophils which migrate to lymph nodes modulates CD4+ T cell response by a PD-L1 dependent mechanism. Frontiers in Immunology, 2019; 10: 105. doi: 10.3389/fimmu.2019.00105
43.    Heeb LE, Egholm C, Boyman O.  Evolution and function of interleukin-4 receptor signaling in adaptive immunity and neutrophils. Genes and Immunity, 2020; 21: 1-7.
44.    Leech JM, Lacey KA, Mulcahy ME, Medina E, McLoughlin RM. IL-10 plays opposing roles during Staphylococcus aureus systemic and localized infections. The Journal of Immunology, 2017; 198(6): 2352-2365. doi: 10.4049/jimmunol.1601018.
45.    Zhang Z, Clarke TB, Weiser JN. Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. Journal of Clinical Investiation, 2009; 119: 1899–1909. doi: 10.1172/JCI36731
46.    Onishi RM, Gaffen SL. Interleukin‐17 and its target genes: mechanisms of interleukin‐17 function in disease. Immunology, 2010; 129(3): 311-321.  doi: 10.1111/j.1365-2567.2009.03240.x.

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