ly inhibited the activation of bacterial au-tolysis induced either by cationic agents orby beta-lactam antibiotics [4, 5, 6, 7].Therefore, it is highly likely that polycat-ions of plasma and leukocyte origins mightbe actively involved in the pathophysiolo-gy of post-infectious sequelae by their ca-pacity to induce a massive release of high-ly phlogistic lipoteichoic acid [7] endotox-in, lipoprotein, and peptidoglycan [8].

Combinations among these agentsmight act on mononuclear cells to generatereactive oxygen species, NO, NOO-, hy-drolases, and also to activate the coagula-tion, complement, and cytokine cascades,all involved in septic shock. Based on theabove arguments, it is tempting to specu-late that the failure to depress early bacteri-olysis in the bloodstream might be themain cause for the inability to cope withthe multiple synergistic interactions lead-ing to post-infectious sequelae [9]. Theclinical use of polyanions when combinedwith mutli drug strategies might thereforebe recommended as potent anti-bacteriolyt-ic and anti-inflammatory agents [10]. It isenigmatic why publications that have pro-posed the role of polycations in bacterioly-sis and the possibility to inhibit its unto-ward effects by polyanions, findings so rel-evant to the patholysiology of post-infec-tious sequelae, are consistently disregarded[11] either in basic science publications onthe bactericidal effects of polycations or inthe clinical literature dealing with post-in-fectious sequelae.

References

1. Bichowski-Slominski L, Berger A,Kurtz J, Katchalski E (1956) The anti-bacterial action of some basic aminoacids copolymers. Arch Biochem Bio-phys 65:400–413

2. Zeya HI, Spitznagel JK (1963) Anti-bacterial and enzyme basic proteinsfrom leukocyte lysosomes. Science142:1085–1087

3. Elsbach P (1998) The bacterial /perme-ability – increasing (BPI) in antibacte-rial defense. J Leuk Biol 64:14–18

4. Ginsburg I (1987) Cationic polyelec-trolytes: a new look at their roles as op-sonins, as stimulators of the respiratoryof in leukocytes in bacteriolysis, and asmodulators of immune complex diseas-es. Inflammation 11:489–515

5. Ginsburg I (1988) The biochemistry ofbacteriolysis: facts, paradoxes andmyths. Microb Sci 5:137–142

6. Ginsburg I (2002) The role of bacteri-olysis in the pathophysiology of in-flammation, infection and post-infec-tious sequelae. APMIS (in press)

7. Ginsburg I (2002) Role of lipoteichoicacid in infection and inflammation.Lancet Infect Dis 2:171–179

8. Sriskandan S, Cohen J (1999) Gram-positive sepsis: mechanisms and differ-ences from Gram-negative sepsis. InfDis Clin North Am 13:397–412

9. Ginsburg I (2001) Hypothesis: is a fail-ure to prevent bacteriolysis and thesynergy among microibial and host-de-rived pro-inflammatory agonists themain contributory factors to the patho-genesis of post-infectious sequelae? In-flammation 25:1–10

10. Ginsburg I (1999) Multidrug strategiesare necessary to inhibit the synergisticmechanisms causing tissue damage andorgan failure in post infectious seque-lae. Inflammopharmacology 7:207–217

11. Ginsburg I (2001) The disregard syn-drome: a menace to honest science?Scientist 10:51

I. Ginsburg (✉ )Department of Oral Biology, Hebrew University, Hadassah Faculty of Dental Medicine 91120,Jerusalem, Israele-mail: ginsburg@cc.huji.ac.ilTel.: +972-2-6758583Fax: +972-2-6758583

Intensive Care Med (2002) 28:1188DOI 10.1007/s00134-002-1385-4 C O R R E S P O N D E N C E

Isaac Ginsburg

Cationic polyelectrolytesfrom leukocytes might kill bacteria by activating their autolytic systems: enigmatically, the relevanceof this phenomenon to post-infectious sequelaeis disregarded

Received: 1 December 2000Accepted: 5 April 2002Published online: 5 July 2002© Springer-Verlag 2002

Linear polymers of lysine and arginine,phagocyte-derived lysozyme, PLA, elas-tase, cathepsin G, myeloperoxidases, nu-clear histone and bacterial/permeability-en-hancing peptide (BPI) and defensins allpossess bactericidal activities [1, 2, 3, 4, 5,6]. The highly cationic BPI and defensinsmight kill Gram-negatives primarily by de-polarizing their outer membrane to en-hance its permeability [3]. However, it hadalso been proposed that many of thesepolycations might also function as “TrojanHorses” to disrupt the intracellular regula-tion of the autolytic wall enzyme systems(muramidases).This can lead to cleavage ofthe peptidoglycan, to bacteriolysis, and tocell death [4, 5, 6].The highly cationic, ly-sozyme, PLA2, and elastase probably donot function solely as enzymes, but ratheras highly cationic agents. The bactericidaland bacteriolytic effects of polycationsmight therefore mimic the bacteriolytic ef-fects caused by beta-lactam antibiotics.Sulfated compounds (heparin, dextran sul-fate, polyaenthole sulfonate) very efficient-